1,2-Dichloroethane → N-Boc-Tyr(Bn)-Asn-Trp-NH(CH2)4NHBoc

HRID 2074361Notes

Reaction equation

HRID 2074361 reaction equation
[NH2:1][C@H:2]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[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:28]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[C@H:29]([C:45]([NH:47][C@H:48]([C:53](O)=[O:54])[CH2:49][C:50](=[O:52])[NH2:51])=[O:46])[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:33][CH:32]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl.CN(C=O)C>[NH:28]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[C@H:29]([C:45]([NH:47][C@H:48]([C:53]([NH:1][C@H:2]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[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:54])[CH2:49][C:50](=[O:52])[NH2:51])=[O:46])[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 16735218Trp-NH(CH2)4NHBocHCID 57611773N-Boc-Tyr(Bn)-Asn-OH

Product 1

HCID 16736551N-Boc-Tyr(Bn)-Asn-Trp-NH(CH2)4NHBocYield 28.4%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

compound SP323C2. Same procedure as above with Trp-NH(CH2)4NHBoc (108.7 mg, 0.29 mmol), N-Boc-Tyr(Bn)-Asn-OH (140.9 mg, 0.29 mmol), EDC (61.8 mg, 0.32 mmol) and HOBt (43.6 mg, 0.32 mmol) in CH2Cl2/DMF (2 mL, 1/1). The crude residue was purified by flash column chromatography on silica gel (2-6% MeOH/CH2Cl2) to give an white solid (69.3 mg, 28%). 1H NMR (300 MHz, DMSO-d6) δ 1.18-1.37 (m, 4H, 2 CH2 putrescine), 1.28 (s, 9H, (CH3)3), 1.37 (s, 9H, (CH3)3), 2.42-3.2 (m, 10H, CH2 Tyr, CH2 Trp, CH2 Asn, 2 CH2 putrescine), 4.1 (m, 1H, CHα), 4.36 (m, 1H, CHα), 4.53 (m, 1H, CHα), 5.03 (s, 2H, CH2 (Bn)), 6.71 (m, 1H), 6.8-7.53 (m, 17H), 7.84 (m, 1H), 8.01 (d, J=9 Hz, 1H), 8.13 (d, J=7.6 Hz, 1H), 10.73 (s, 1H). 13C NMR (75 MHz, DMSO-d6) δ 26.4, 27 (2 CH2 putrescine), 27.4 (CH2 Trp), 28.4 ((CH3)3), 36.6, 37.2 (CH2 Tyr, CH2 Asn), 38.4, 39.4 (2 CH2 putrescine), 49.8, 54, 55.9 (CHα Tyr, Asn, Trp), 69.2 (CH2 (Bn)), 77.5, 78.2 (C(CH3)3), 110.2, 111.3, 114.4, 118.3, 120.9, 123.6, 127.4, 127.7, 127.9, 128.5, 130.3, 130.4, 136.1, 137.4 (19 aromatic C), 155.4, 155.7, 157 (Car-O, 2 CO carbamate), 170.7, 170.9, 171.8, 172.1 (4 CO amide). Anal. Calcd. for C45H59N7O9: C, 64.19; H, 7.06; N, 11.64. Found: C, 63.97; H, 7.05; N, 11.76.

Workup

  1. customThe crude residue was purified by flash column chromatography on silica gel (2-6% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-471346bfaf9947e0928d3d2f5abfa9f1
Source dataset
uspto-grants-2011_04
Patent number
US07919468B2

Reaction notes

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