Paper
26FN
Organic & Biomolecular Chemistry
+
1
C
16
H
4
O
4
357.2, [M + Na] calcd for C16
H25FN
4
NaO
4
379.1,
H NMR (400 MHz, CDCl
3
) δ: 5.10 (d, J = 7.8 Hz, 1H, NH),
+
[2M + Na] calcd for C H F N NaO 735.4, found (relative 4.13 (br, 1H, CH), 3.60 (br, 2H, CH N), 3.25 (br, 2H, NCH ),
3
2
50
2
8
8
2
2
+
+
intensity) 157.1 (100) [M-2Boc + H] , 257.1 (33) [M-Boc + H] , 2.49 (br, 2H, NCH
2
), 2.26 (s, 6H, 2 × CH
3
), 1.88–1.72 (m, 1H,
+
+
+
3
57.1 (10) [M + H] , 379.1 (81) [M + Na] , 735.3 (49) [2M + Na] . CH
tert-Butyl
pyrazol-1-yl)methylidene} carbamate, 3e. (Procedure A) Yield
2
2
), 1.66–1.52 (m, 3H, 2 × CH ), 1.43 (s, 9H, tBu), 1.42 (s,
N-{{benzyl[(tert-butoxy)carbonyl]amino}(1H- 18H, 2 × tBu), 1.40 (s, 9H, tBu).
1
3
C NMR (100 MHz, CDCl
152.3 (2 × CO), 82.0 (2 × CtBu), 79.6 (CtBu), 78.8 (CtBu), 58.4
H NMR (400 MHz, CDCl ) δ: 7.59–7.58 (m, 2H, ArH), (CH N), 53.6 (CH), 45.5 (NCH ), 45.3 (2 × CH ), 42.5 (NCH ),
3 3
) δ: 171.5 (2 × CO), 155.3 (CN ),
9
f
9% (0.398 g), R 0.42 (n-hexane/AcOEt 75 : 25).
1
3
2
2
3
2
7
2
1
2
.41–7.35 (m, 2H, ArH), 7.27–7.14 (m, 3H, ArH), 6.26 (dd, J = 30.5 (CH ), 28.3 (tBu), 28.2 (tBu), 28.1 (tBu), 27.9 (tBu), 24.8
.7, 1.6 Hz, 1H, ArH), 4.85 (s, 2H, CH
2
N), 1.39 (s, 9H, tBu), (CH
2
).
+
+
.17 (s, 9H, tBu).
ESI MS m/z: [M + H] calcd for C H N O 602.4, [M + Na]
2
9
56 5 8
1
3
C (100 MHz, CDCl
42.9 (CAr), 136.6 (CAr), 129.9 (CAr), 128.6 (CAr), 128.5 (2 × CAr), (100) [M + H] , 624.4 (10) [M + Na] .
27.7 (2 × C ), 108.7 (C ), 83.1 (CtBu), 82.3 (CtBu), 52.2 tert-Butyl 5-{2,3-bis(tert-butoxycarbonyl)-3-[2-(methylthio)-
ethyl]guanidine}-2-[(tert-butoxycarbonyl)amino]pentanoate, 5c.
(Procedure B) Yield 99% (0.601 g), R 0.28 (n-hexane/eAcOEt
Na] calcd for 80 : 20).
3 3 55 5 8
) δ: 157.5 (CO), 152.5 (CO), 144.4 (CN ), calcd for C29H N NaO 624.4, found (relative intensity)602.4
+
+
1
1
Ar
Ar
(CH
2
N), 27.9 (tBu), 27.7 (tBu).
ESI MS m/z: [M + H] calcd for C21
+
+
H
29
N
4
O
+
4
401.2, [M + Na]
f
+
calcd for C H N NaO 423.2, [2M
2
1
28
4
4
2
0
C
42
+
H
56
N
8
NaO
8
823.4, found (relative intensity) 401.2 (21) [M +
[α]
D
= −6.00 (c 1.0, MeOH).
+
+
1
1
] , 423.2 (39) [M + Na] , 823.4 (100) [2M + Na] .
H NMR (400 MHz, CDCl ) δ: 5.04 (d, J = 7.7 Hz, 1H, NH),
3
tert-Butyl N-{{[(tert-butoxy)carbonyl]imino}(1H-pyrazol-1-yl)- 4.12 (s, 1H, CH), 3.80 (t, J = 6.8 Hz, 2H, SCH ), 3.24 (br, 2H,
2
methyl}(2-methoxyethyl)carbamate, 3f. (Procedure A) Yield NCH
2
), 2.61 (t, J = 6.9 Hz, 2H, CH
1.84–1.71 (m, 1H, CH ), 1.68–1.49 (m, 3H, 2 × CH
H NMR (400 MHz, CDCl ) δ: 7.87 (s, 1H, ArH), 7.61 (d, J = 9H, tBu), 1.41 (s, 9H, tBu), 1.40 (s, 9H, tBu), 1.37 (s, 9H, tBu).
2
N), 2.03 (s, 3H, CH
3
S),
9
5% (0.349 g), R
f
0.35 (n-hexane/AcOEt 75 : 25).
2
2
), 1.42 (s,
1
3
1
3
1
2
1
.0 Hz, 1H, ArH), 6.33 (dd, J = 2.7, 1.6 Hz, 1H, ArH), 3.84 (m,
H, CH N), 3.58 (t, J = 5.6 Hz, 2H, OCH ), 3.20 (s, 3H, CH O), CO), 152.9 (CN
.42 (s, 9H, tBu), 1.19 (s, 9H, tBu). (CtBu), 53.5 (CH), 46.1 (SCH ), 43.5 (NCH ), 33.1 (CH N), 30.3
C NMR (100 MHz, CDCl
3
) δ: 171.4 (2 × CO), 155.3 (2 ×
2
2
3
3
), 82.6 (CtBu), 82.1 (CtBu), 79.7 (CtBu), 79.2
2
2
2
1
3
C (100 MHz, CDCl
42.9 (CAr), 129.9 (CAr), 108.6 (CAr), 82.6 (CtBu), 82.1 (CtBu), 15.0 (CH
9.9 (CH N), 58.3 (CH O), 47.6 (OCH ), 27.8 (tBu), 27.6 (tBu). ESI MS m/z: [M + H] calcd for C H N O S 605.4,
3
) δ: 157.4 (CO), 152.3 (CO), 144.6 (CN
3
), (CH
2
), 28.3 (tBu), 28.2 (tBu), 28.1 (tBu), 28.0 (tBu), 24.9 (CH
2
),
1
6
3
S).
+
2
3
2
28 53 4 8
+
+
+
ESI MS m/z: [M + H] calcd for C17
calcd for NaO 391.2, [2M
C H N NaO 759.4, found (relative intensity) 369.2 (50) [M +
H
29
N
4
O
+
5
369.2, [M + Na]
[M + Na] calcd for C28
Na] calcd for intensity) 605.4 (100) [M + H] , 627.4 (10) [M + Na] .
H
52
+
N
4
NaO
8
S 627.4, found (relative
+
+
C
17
H
28
N
4
5
tert-Butyl
5-[2,3-bis(tert-butoxycarbonyl)-3-(2-fluoroethyl)-
3
4
+
56 8
10
+
+
H] , 391.2 (74) [M + Na] , 759.4 (100) [2M + Na] .
guanidino]-2-[(tert-butoxycarbonyl)amino]pentanoate,
5d.
tert-Butyl 8-(tert-butoxycarbonyl)-14-[(tert-butoxycarbonyl)- (Procedure B) Yield 99% (0.570 g), R
amino]-9-[(tert-butoxycarbonyl)imino]-2,2,5-trimethyl-4-oxo-3- 80 : 20).
f
0.35 (n-hexane/AcOEt
2
0
oxa-5,8,10-triazapentadecan-15-oate, 5a. (Procedure B) Yield
7% (0.532 g), R 0.25 (dichloromethane/methanol 98 : 2).
α] = +6.00 (c 1.0, CHCl3).
[α]
D
= −9.00 (c 1.0, MeOH).
1
7
f
H NMR (400 MHz, DMSO, 80 °C) δ: 4.54 (dt, JF–H = 47.3 Hz,
JH–H = 5.4 Hz, 2H, FCH ), 3.88–3.79 (m, 1H, CH), 3.66 (dt,
F–H = 23.7 Hz, JH–H = 5.4 Hz, 2H, CH
2
0
[
D
2
1
H NMR (400 MHz, DMSO, 80 °C) δ: 7.88 (br, 1H, NH), 6.56
J
2
N), 3.15 (t, J = 6.4 Hz, 2H,
), 1.44
(
br, 1H, NH), 3.88–3.79 (m, 1H, CH), 3.48 (t, J = 6.8 Hz, 2H, NCH
2
), 1.78–1.68 (m, 1H, CH ), 1.66–1.54 (m, 3H, CH
2
2
NCH ), 3.35 (t, J = 6.8 Hz, 2H, CH N), 3.15 (br, 2H, NCH ), 2.82 (s, 9H, tBu), 1.43 (s, 9H, tBu), 1.41 (s, 18H, 2 × tBu).
2
2
2
1
3
(
1
1
s, 3H, CH
3
N), 1.82–1.67 (m, 1H, CH
2
), 1.67–1.54 (m, 3H, CH
2
),
C NMR (100 MHz, CDCl
), 82.7 (CtBu), 82.0 (CtBu), 81.9 (d, JF–C = 168.7
Hz, FCH ), 79.6 (CtBu), 79.4 (CtBu), 53.4 (CH), 48.0 (d, J
3
) δ: 171.4 (2 × CO), 155.3 (2 ×
.44 (s, 9H, tBu), 1.43 (s, 9H, tBu), 1.42 (s, 9H, tBu), 1.41 (s, CO), 152.6 (CN
8H, 2 × tBu).
3
=
F–C
2
1
3
C NMR (100 MHz, DMSO, 80 °C) δ: 171.9 (2 × CO), 160.0 20.0 Hz, CH
2
N), 43.4 (NCH
2
), 30.2 (CH
).
F NMR (376 MHz, DMSO) δ: −220.73 (tt, J = 47.9, 23.8 Hz).
2
), 28.3 (tBu), 28.2 (tBu),
(
(
(
(
CN
3
), 155.7 (CO), 152.8 (2 × CO), 81.3 (CtBu), 80.8 (CtBu), 79.3 28.1 (tBu), 27.9 (tBu), 24.9 (CH
2
1
9
CtBu), 78.7 (CtBu), 78.3 (CtBu), 54.9 (CH), 47.6 (NCH ), 45.3
2
+
CH
2
N), 42.4 (NCH
2
), 34.8 (CH
3
N), 29.0 (CH
2
), 28.7 (tBu), 28.6
).
ESI MS m/z: [M + H] calcd for C H N O 688.4, found
ESI MS m/z: [M + H] calcd for C27
(relative intensity) 577.4 (100) [M + H] .
H
50FN
4
O
8
577.4, found
+
tBu), 28.5 (tBu), 28.4 (tBu), 28.2 (tBu), 25.3(CH
2
+
tert-Butyl
5-[3-benzyl-2,3-bis(tert-butoxycarbonyl)guani-
3
3
62 5 10
+
(
relative intensity) 688.4 (100) [M + H] .
tert-Butyl 5-{2,3-bis(tert-butoxycarbonyl)-3-[2-(dimethyl- cedure B) Yield 69% (0.427 g), R
amino)ethyl]guanidino}-2-[(tert-butoxycarbonyl)amino]-
pentanoate, 5b. (Procedure B) Yield 97% (0.599 g), R 0.16
dichloromethane/methanol 96 : 4).
dino]-2-[(tert-butoxycarbonyl)amino]pentanoate,
5e. (Pro-
f
0.31 (n-hexane/AcOEt 50 : 50).
2
0
[α] = −4.00 (c 1.0, MeOH).
D
1
f
H NMR (400 MHz, CDCl
3
) δ: 7.28–7.12 (m, 6H, ArH, NH),
(
4.90 (br, 1H, NH), 4.78 (s, 2H, CH
2
N), 4.01 (br, 1H, CH), 2.97
2
0
[
α] = +9.00 (c 1.0, CHCl3).
(br, 2H, NCH ), 1.53–1.23 (m, 40H, 2 × CH , 4 × tBu).
D
2
2
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2015