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

HRID 2074353Notes

Reaction equation

HRID 2074353 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:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[C@H:23]([C:39]([NH:41][C@H:42]([C:47](O)=[O:48])[CH2:43][CH:44]([CH3:46])[CH3:45])=[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.CCOCC>[NH:22]([C:50]([O:52][C:53]([CH3:55])([CH3:54])[CH3:56])=[O:51])[C@H:23]([C:39]([NH:41][C@H:42]([C:47]([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:48])[CH2:43][CH:44]([CH3:46])[CH3:45])=[O:40])[CH2:24][C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 16735217(S)-2-Amino-3-(1H-indol-3-yl)-N-phenylpropanamideHCID 57611771N-Boc-Tyr(Bn)-Leu-OH

Product 1

HCID 16736958N-Boc-Tyr(Bn)-Leu-Trp-NHPhYield 75.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

compound A424P. Same procedure as above with Trp-NHPh (67.6 mg, 0.242 mmol), N-Boc-Tyr(Bn)-Leu-OH (117 mg, 0.242 mmol), EDC (49 mg, 0.25 mmol) and HOBt (35 mg, 0.25 mmol) in CH2Cl2/DMF (3.6 mL, 1/1). The crude residue was dissolved in ether and precipitated with heptane to give a beige solid (135.6 mg, 75%). 1H NMR (300 MHz, DMSO-d6) δ 0.83 (d, 3H, J=6.4 Hz, CH3), 0.87 (d, 3H, J=6.4 Hz, CH3), 1.22-1.44 (m, 2H, CH2 Leu), 1.30 (s, 9H, (CH3)3), 1.44 (m, 1H, CH Leu), 2.46-2.89 (m, 2H, CH2), 3.13 (m, 2H, CH2), 4.12 (m, 1H, CHα), 4.38 (m, 1H, CHα), 4.70 (m, 1H, CHα), 5.02 (s, 2H, CH2 (Bn)), 6.87-7.58 (m, 20H, 19 aromatic H and NH Boc), 7.94 (d, J=8.2 Hz, 1H), 8.17 (d, J=7.5 Hz, 1H), 10.0 (s, 1H, NH), 10.83 (s, 1H, NH). 13C NMR (75 MHz, DMSO-d6) δ 21.5, 23.1, 23.9 (CH—(CH3)2), 27.7 (CH2 Trp), 28.1 ((CH3)3), 36.2, 40.9 (CH2 Tyr, CH2 Leu), 50.9, 54.1, 55.7 (CHα Tyr, Leu, Tip), 69.0 (CH2 (Bn)), 78.0 (C(CH3)3), 109.6, 111.2, 114.2, 118.2, 118.4, 119.3, 120.8, 123.3, 123.4, 127.3, 127.6, 127.7, 128.3, 128.6, 130.1, 130.3, 135.9, 137.2, 138.8 (25 aromatic C), 155.2, 156.8 (Car-O, CO carbamate), 170, 171.6, 171.9 (3 CO amide). Anal. Calcd. for C44H51N5O6: C, 70.85; H, 6.89; N, 9.39. Found: C, 70.52; H, 7.10; N, 9.33.

Workup

  1. customprecipitated with heptane

Sources & evidence

ORD record
ord-bd012f1617de481998088a6da2359d68
Source dataset
uspto-grants-2011_04
Patent number
US07919468B2

Reaction notes

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