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

HRID 2074362Notes

Reaction equation

HRID 2074362 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:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[C@H:29]([C:45]([NH:47][C@H:48]([C:61](O)=[O:62])[CH2:49][CH2:50][CH2:51][CH2:52][NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])=[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:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[C@H:29]([C:45]([NH:47][C@H:48]([C:61]([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:62])[CH2:49][CH2:50][CH2:51][CH2:52][NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])=[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 57611779N-Boc-Tyr(Bn)-Lys(Boc)-OH

Product 1

HCID 16736779N-Boc-Tyr(Bn)-Lys(Boc)-Trp-NH(CH2)4NHBocYield 65.8%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

compound SP308P. Same procedure as above with Trp-NH(CH2)4NHBoc (152.4 mg, 0.407 mmol), N-Boc-Tyr(Bn)-Lys(Boc)-OH (247.3 mg, 0.407 mmol), EDC (85.8 mg, 0.45 mmol) and HOBt (60.7 mg, 0.45 mmol) in CH2Cl2/DMF (1.8 mL, 1/1). The crude residue was triturated with MeOH/pentane to afford a white solid (255.9 mg, 65%). 1H NMR (300 MHz, DMSO-d6) δ 1.29-1.57 (m, 10H, 3 CH2 Lys, 2 CH2 putrescine), 1.29 (s, 9H, (CH3)3), 1.36 (s, 9H, (CH3)3), 2.64 (m, 1H, CH2 Tyr), 2.86-3.11 (m, 9H, CH2 Lys, CH2 Tyr, CH2 Trp, 2 CH2 putrescine), 4.10 (m, 1H, CHα), 4.26 (m, 1H, CHα), 4.46 (m, 1H, CHα), 5.03 (s, 2H, CH2 (Bn)), 6.70 (broad s, 1H), 6.87-7.4 (m, 15H), 7.56 (d, J=7.6 Hz, 1H), 7.81-7.97 (m, 3H), 10.8 (s, 1H). 13C NMR (75 MHz, DMSO-d6) δ 22.4, 29.2, 32 (3 CH2 Lys), 26.2, 26.7 (2 CH2 putrescine), 27.8 (CH2 Trp), 28, 28.1, 28.2 (3 (CH3)3), 36.3 (CH2 Tyr), 38.2, 39.5, 39.8 (2 CH2 putrescine, CH2 Lys), 52.4, 53.4, 55.8 (CHα Tyr, Lys, Tip), 69 (CH2 (Bn)), 77.2, 78 (2 C(CH3)3), 109.8, 111.1, 114.2, 118.1, 118.4, 120.7, 123.4, 127.3, 127.5, 127.6, 128.3, 130.1, 135.9, 137.1 (19 aromatic C), 154.7, 155.5, 156.7 (Car-O, 2 CO carbamate), 170.7, 171.1, 171.5 (3 CO amide). Anal. Calcd. for C52H73N7O10: C, 65.32; H, 7.70; N, 10.25. Found: C, 65.30; H, 7.64; N, 10.04.

Workup

  1. customThe crude residue was triturated with MeOH/pentane

Sources & evidence

ORD record
ord-581771c57df94a24b5b9842f94942a4f
Source dataset
uspto-grants-2011_04
Patent number
US07919468B2

Reaction notes

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