1,2-Dichloroethane → N-Boc-Tyr(Bn)-Lys(Boc)-Trp-NHPh

HRID 2074355Notes

Reaction equation

HRID 2074355 reaction equation
[NH2:1][C@H:2]([C:13]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[NH:22]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[C@H:23]([C:39]([NH:41][C@H:42]([C:55](O)=[O:56])[CH2:43][CH2:44][CH2:45][CH2:46][NH:47][C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[O:40])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:27][CH:26]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl.CN(C=O)C>[NH:22]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[C@H:23]([C:39]([NH:41][C@H:42]([C:55]([NH:1][C@H:2]([C:13]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1)=[O:56])[CH2:43][CH2:44][CH2:45][CH2:46][NH:47][C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[O:40])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 16735217(S)-2-Amino-3-(1H-indol-3-yl)-N-phenylpropanamideHCID 57611779N-Boc-Tyr(Bn)-Lys(Boc)-OH

Product 1

HCID 16735716N-Boc-Tyr(Bn)-Lys(Boc)-Trp-NHPhYield 63.1%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

compound SP306P. Same procedure as above with Trp-NHPh (99.6 mg, 0.356 mmol), N-Boc-Tyr(Bn)-Lys(Boc)-OH (214 mg, 0.356 mmol), EDC (75.3 mg, 0.392 mmol) and HOBt (53.7 mg, 0.397 mmol) in CH2Cl2/DMF (1.5 mL, 1/1). The crude residue was triturated with MeOH/pentane to afford a white solid (193.5 mg, 63%). 1H NMR (300 MHz, DMSO-d6) δ 1.21-1.62 (m, 6H, 3 CH2 Lys), 1.3 (s, 9H, (CH3)3), 1.36 (s, 9H, (CH3)3), 2.64 (m, 1H, CH2 Tyr), 2.87 (m, 3H, CH2 Lys, CH2 Tyr), 3.05 (dd, J=14.7 Hz, J=7.7 Hz, 1H, CH2 Trp), 3.19 (dd, J=14.7 Hz, J=6.2 Hz, 1H, CH2 Trp), 4.11 (m, 1H, CHα), 4.31 (m, 1H, CHU), 4.71 (m, 1H, CHU), 5.02 (s, 2H, CH2 (Bn)), 6.71 (m, 1H), 6.87-7.42 (m, 17H), 7.58 (m, 3H), 7.9 (d, J=7.3 Hz, 1H), 8.18 (d, J=7.2 Hz, 1H), 10 (s, 1H), 10.8 (s, 1H). 13C NMR (75 MHz, DMSO-d6) δ 22.5, 29.2, 32 (3 CH2 Lys), 27.8 (CH2 Trp), 28.1, 28.2 (2 (CH3)3), 36.3 (CH2 Tyr), 39.8 (CH2 Lys), 52.4, 54.2, 55.8 (CHα Tyr, Lys, Trp), 69.1 (CH2 (Bn)), 77.3, 78.1 (2 C(CH3)3), 109.6, 111.2, 114.3, 118.2, 118.4, 119.4, 120.8, 123.3, 123.4, 127.3, 127.5, 127.7, 128.3, 128.6, 130.1, 130.2, 136, 137.2, 138.8 (25 aromatic C), 155.2, 155.5, 156.8 (Car-O, 2 CO carbamate), 170.1, 171.5, 171.6 (3 CO amide). Anal. Calcd. for C49H60N6O8, 1.5H2O: C, 66.27; H, 7.15; N, 9.46. Found: C, 66.42; H, 6.96; N, 9.34.

Workup

  1. customThe crude residue was triturated with MeOH/pentane

Sources & evidence

ORD record
ord-cc20c21a5e74441a996d0d28d4caad99
Source dataset
uspto-grants-2011_04
Patent number
US07919468B2

Reaction notes

Loading…