δ = 1.13 (d, 3H, J = 6.6 Hz), 1.40 (s, 9H), 1.53 (m, 2H), 1.70 (m,
2H), 1.82 (m, 4H), 3.36 (m, 1H), 3.47 (m, 2H), 4.11 (m, 2H),
4.78 (br, 1H), 6.17 (br, 1H), 6.62 (br, 1H), 7.15 (m, 1H), 7.26 (d,
1H, J = 8.8 Hz), 7.52 (m, 2H), 7.62 (m, 3H), 7.85 (dd, 1H, J =
2.0, 8.8 Hz), 8.39 (d, 1H, J = 2.0 Hz). MS (ESI) 510.3 (M+H)+
7.54 (m, 1H), 7.67 (m, 2H), 7.87 (br, 1H), 8.98 (d, 1H, J = 2.4
Hz). MS (ESI) 495.3 (M+H)+
4.1.38. tert-Butyl ((1S,4s)-4-((6-(3-fluorophenyl)-2-(((R)-1-
hydroxypropan-2-yl)amino)pyrido[2,3-d]pyrimidin-4-
yl)amino)cyclohexyl)carbamate (33b)
4.1.33. tert-Butyl ((1S,4s)-4-((6-(3-fluorophenyl)-2-(((R)-1-
methoxypropan-2-yl)amino)quinazolin-4-
yl)amino)cyclohexyl)carbamate (32c)
Prepared from 27b (55.3 mg, 0.112 mmol) and 3-
fluorophenylboronic acid (18.74 mg, 0.134 mmol) by general
1
procedure F. Slight brown amorphous (40.8 mg, 72%). H NMR
Prepared from 26c (86.0 mg, 0.169 mmol) and 3-
(CDCl3) δ = 1.28 (d, 3H, J = 6.8 Hz), 1.45 (s, 9H), 1.78 (m, 6H),
1.93 (m, 2H), 3.66 (dd, 1H, J = 7.2, 10.9 Hz), 3.72 (br, 1H), 3.81
(m, 1H), 4.26 (br, 1H), 4.38 (br, 1H), 4.69 (br, 1H), 5.20 (br, 1H),
5.73 (br, 1H), 7.08 (m, 1H), 7.29 (m, 1H), 7.37 (m, 1H), 7.44 (m,
1H), 7.92 (br, 1H), 8.96 (d, 1H, J = 2.4 Hz). MS (ESI) 511.3
(M+H)+
fluorophenylboronic acid (28.4 mg, 0.203 mmol) by general
1
procedure F. White solid (79.2 mg, 89%). H NMR (CDCl3) δ =
1.30 (d, 3H, J = 6.7 Hz), 1.46 (s, 9H), 1.75 (m, 4H), 1.82 (m, 2H),
1.94 (m, 2H), 3.40 (s, 3H), 3.44 (dd, 1H, J = 5.2, 9.2 Hz), 3,52
(dd, 1H, J = 4.5, 9.2 Hz), 3.73 (m, 1H), 4.33 (m, 2H), 4.63 (br,
1H), 5.10 (br, 1H), 5.49 (br, 1H), 7.04 (m, 1H), 7.31 (m, 1H),
7.40 (m, 2H), 7.49 (d, 1H, J = 8.7 Hz), 7.57 (d, 1H, J = 2.0 Hz),
7.74 (dd, 1H, J = 2.0, 8.7 Hz). MS (ESI) 524.3 (M+H)+
4.1.39. tert-Butyl ((1S,4s)-4-((6-(3-fluorophenyl)-2-(((R)-1-
hydroxypropan-2-yl)amino)pyrido[3,4-d]pyrimidin-4-
yl)amino)cyclohexyl)carbamate (34b)
4.1.34. tert-Butyl ((1R,4s)-4-((6-(3-Fluorophenyl)-2-(((S)-1-
methoxypropan-2-yl)amino)quinazolin-4-
yl)amino)cyclohexyl)carbamate (32d)
Prepared from 28b (58.2 mg, 0.129 mmol) and 3-
fluorophenylboronic acid (21.67 mg, 0.155 mmol) by general
procedure F. White solid, which was recrystallized from AcOEt-
1
Prepared from 26d (53.0 mg, 0.104 mmol) and 3-
fluorophenylboronic acid (17.50 mg, 0.125 mmol) by general
procedure F. 1H NMR (CDCl3) δ = 1.30 (d, 3H, J = 6.7 Hz), 1.46
(s, 9H), 1.80 (m, 6H), 1.94 (m, 2H), 3.41 (s, 3H), 3.44 (m, 1H),
3.52 (dd, 1H, J = 4.4, 9.2 Hz), 3.72 (m, 1H), 4.35 (m, 2H), 4.63
(m, 1H), 5.12 (br, 1H), 5.45 (br, 1H), 7.04 (m, 1H), 7.34 (m, 1H),
7.42 (m, 2H), 7.48 (d, 1H, J = 8.7 Hz), 7.56 (d, 1H, J = 1.9 Hz),
7.74 (dd, 1H, J = 1.9, 8.7 Hz). MS (ESI) 524.3 (M+H)+
hexane (39.5 mg, 60%). H NMR (CDCl3) δ = 1.30 (d, 3H, J =
6.8 Hz), 1.46 (s, 9H), 1.80 (m, 6H), 1.94 (m, 2H), 3.67 (dd, 1H, J
= 7.7, 10.8 Hz), 3.73 (m, 1H), 3.82 (dd, 1H, J = 2.7, 10.8 Hz),
4.26 (m, 2H), 4.65 (m, 1H), 5.15 (br, 1H), 5.62 (br, 1H), 7.09 (m,
1H), 7.44 (m, 1H), 7.58 (s, 1H), 7.72 (m, 1H), 7.78 (m, 1H), 8.90
(s, 1H). MS (ESI) 511.3 (M+H)+
4.1.40. tert-Butyl ((1S,4s)-4-((6-(3-fluorophenyl)-2-(((R)-1-
methoxypropan-2-yl)amino)pyrido[3,2-d]pyrimidin-4-
yl)amino)cyclohexyl)carbamate (35c)
4.1.35.
tert-Butyl
((1s,4s)-4-((6-(3-Fluorophenyl)-2-((2-
methoxyethyl)amino)quinazolin-4-
yl)amino)cyclohexyl)carbamate (32e)
Prepared from 29c (92.5 mg, 0.199 mmol) and 3-
fluorophenylboronic acid (33.4 mg, 0.239 mmol) by general
1
Prepared from 26e (88.3 mg, 0.179 mmol) and 3-
procedure F. White solid (105.3 mg, quant). H NMR (DMSO-
fluorophenylboronic acid (30.0 mg, 0.214 mmol) by general
procedure F. Slight yellow solid (81.6 mg, 90%). H NMR
d6) δ = 1.14 (d, 3H, J = 6.7 Hz), 1.40 (s, 9H), 1.64 (m, 6H), 1.91
(m, 2H), 3.25 (dd, 1H, J = 6.6, 9.3 Hz), 3.28 (s, 3H), 3.44 (dd, 1H,
J = 5.8, 9.3 Hz), 3.57 (m, 1H), 4.14 (m, 1H), 4.27 (m, 1H), 6.67
(br, 2H), 7.25 (m, 1H), 7.41 (br, 1H), 7.57 (m, 2H), 8.04 (d, 1H, J
= 8.9 Hz), 8.08 (m, 1H), 8.18 (d, 1H, J = 8.9 Hz). MS (ESI)
525.3 (M+H)+
1
(CDCl3) δ = 1.46 (s, 9H), 1.72 (m, 4H), 1.82 (m, 2H), 1.94 (m,
2H), 3.41 (s, 3H), 3.61 (t, 2H, J = 5.2 Hz), 3.71 (q, 2H, J = 5.2
Hz), 3.73 (m, 1H), 4.30 (m, 1H), 4.63 (br, 1H), 5.27 (br, 1H),
5.47 (br, 1H), 7.04 (m, 1H), 7.31 (m, 1H), 7.40 (m, 2H), 7.51 (d,
1H, J = 8.7 Hz), 7.57 (d, 1H, J = 2.0 Hz), 7.75 (dd, 1H, J = 2.0,
8.7 Hz). MS:510.3 (M+H)+
4.1.41.
(R)-2-((4-(((1r,4R)-4-Aminocyclohexyl)amino)-6-
phenylquinazolin-2-yl)amino)propan-1-ol (36b) : General
procedure G
4.1.36.
tert-Butyl
((1s,4s)-4-((6-(3-Fluorophenyl)-2-((2-
hydroxyethyl)(methyl)amino)quinazolin-4-
yl)amino)cyclohexyl)carbamate (32f)
A solution of 30b (101.9 mg, 0.207 mmol) and TFA (2 mL) in
CH2Cl2 (2 mL) was stirred at room temperature for 1h. The
solvent was removed and the residue was diluted with CHCl3 (3
mL) and 4N NaOH (3 mL). The mixture was stirred at room
temperature for 30 min. The organic layer was washed with sat.
NaCl, then dried over MgSO4 and filtered. The solvent was
evaporated to give the title compound without further purification
Prepared from 26f (101.0 mg, 0.204 mmol) and 3-
fluorophenylboronic acid (34.3 mg, 0.245 mmol) by general
procedure F. Slight yellow solid (101.2 mg, 97%). H NMR
(CDCl3) δ = 1.46 (s, 9H), 1.71 (m, 2H), 1.83 (m, 4H), 1.96 (m,
2H), 3.29 (s, 3H), 3.73 (m, 1H), 3.83 (m, 2H), 3.92 (m, 2H), 4.29
(m, 1H), 4.64 (br, 1H), 5.57 (br, 1H), 7.04 (m, 1H), 7.30 (m, 1H),
7.42 (m, 2H), 7.48 (d, 1H, J = 8.7 Hz), 7.56 (d, 1H, J = 2.0 Hz),
7.74 (dd, 1H, J = 2.0, 8.7 Hz). MS (ESI) 510.3 (M+H)+
1
1
as white amorphous (79.4 mg, 98%). H NMR (DMSO-d6) δ =
1.14 (d, 3H, J = 6.6 Hz), 1.15 (m, 2H), 1.47 (m, 4H), 1.83 (m,
2H), 1.94 (m, 2H), 2.57 (m, 1H), 3.37 (m, 1H), 3.48 (m, 1H),
4.07 (m, 2H), 4.80 (m, 1H), 6.13 (br, 1H), 7.26 (d, 1H, J = 8.7
Hz), 7.32 (m, 1H), 7.46 (m, 2H), 7.62 (br, 1H), 7.75 (m, 2H),
7.80 (dd, 1H, J = 2.0, 8.7 Hz), 8.33 (d, 1H, J = 2.0 Hz). MS (ESI)
392.3 (M+H)+
4.1.37.
tert-Butyl
((1s,4s)-4-((6-(3-fluorophenyl)-2-
(isopropylamino)pyrido[2,3-d]pyrimidin-4-
yl)amino)cyclohexyl)carbamate (33a)
Prepared from 27a (204.0 mg, 0.426 mmol) and 3-
4.1.42.
(R)-2-((4-(((1r,4R)-4-Aminocyclohexyl)amino)-6-(3-
fluorophenylboronic acid (71.4 mg, 0.511 mmol) by general
fluorophenyl)quinazolin-2-yl)amino)propan-1-ol (37b)
1
procedure F. Yellow amorphous (181.2 mg, 86%). H NMR
(CDCl3) δ = 1.28 (d, 6H, J = 6.5 Hz), 1.45 (s, 9H), 1.83 (m, 8H),
3.73 (m, 1H), 4.28 (m, 1H), 4.46 (m, 1H), 4.62 (m, 1H), 5.00 (br,
1H), 5.49 (br, 1H), 7.08 (m, 1H), 7.30 (m, 1H), 7.47 (m, 4H),
Prepared from 31b (83.0 mg, 0.163 mmol) by general procedure
G. White amorphous (59.3 mg, 89%). H NMR (DMSO-d6) δ =
1.14 (d, 3H, J = 6.6 Hz), 1.15 (m, 2H), 1.48 (m, 4H), 1.84 (m,
1
2H), 1.96 (m, 2H), 2.59 (m, 1H), 3.36 (m, 1H), 3.49 (m, 1H),