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

HRID 2074360Notes

Reaction equation

HRID 2074360 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][CH:50]([CH3:52])[CH3:51])=[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.CCN(CC)CC>C(Cl)Cl.CN(C=O)C>[NH:28]([C:56]([O:58][C:59]([CH3:61])([CH3:60])[CH3:62])=[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][CH:50]([CH3:52])[CH3:51])=[O:46])[CH2:30][C:31]1[CH:32]=[CH:33][C:34]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:35][CH:36]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 16735218Trp-NH(CH2)4NHBocHCID 57611771N-Boc-Tyr(Bn)-Leu-OH

Product 1

HCID 16737909N-Boc-Tyr(Bn)-Leu-Trp-NH(CH2)4NHBocYield 33.1%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

compound SP296P. Same procedure as above with Trp-NH(CH2)4NHBoc (264.7 mg, 0.706 mmol), N-Boc-Tyr(Bn)-Leu-OH (342.6 mg, 0.707 mmol), EDC (150.3 mg, 0.784 mmol), HOBt (105.3 mg, 0.78 mmol) and NEt3 (0.39 mL, 2.8 mmol) in CH2Cl2/DMF (3 mL, 1/1). The crude residue was triturated with Et2O/pentane to give a white solid (196.7 mg, 33%). 1H NMR (300 MHz, DMSO-d6) δ 0.82 (d, J=6.2 Hz, 3H, CH3 Leu), 0.86 (d, S=6.2 Hz, 3H, CH3 Leu), 1.25-1.41 (m, 4H, 2 CH2 putrescine), 1.29 (s, 9H, (CH3)3), 1.36 (s, 9H, (CH3)3), 2.59-3.1 (m, 8H, CH2 Tyr, CH2 Trp, 2 CH2 putrescine), 4.09 (m, 1H, CHα), 4.32 (m, 1H, CHα), 4.44 (m, 1H, CHα), 5.02 (s, 2H, CH2 (Bn)), 6.71 (m, 1H), 6.87-7.4 (m, 14 aromatic H), 7.54 (d, J=7.7 Hz, 1H), 7.79 (m, 1H), 7.94 (m, 2H), 10.8 (s, 1NH). 13C NMR (75 MHz, DMSO-d6) δ 20.3, 21.8, 22.7 (2 CH3, CH Leu), 24.9, 25.5 (2 CH2 putrescine), 26.7 (CH2 Trp), 26.9, 27 (2 (CH3)3), 34.9 (CH2 Tyr), 37, 39.2, 39.7 (2 CH2 putrescine, CH2 Leu), 49.8, 52.2, 54.6 (CHα Ala, Tyr, Trp), 67.8 (CH2 (Bn)), 76, 76.8 (2 C(CH3)3), 108.6, 109.9, 113, 116.9, 117.1, 119.5, 122.1, 126.1, 126.3, 126.5, 127.1, 128.9, 129.1, 134.7, 136 (19 aromatic C), 154, 154.3, 155.6 (Car-O, 2 CO carbamate), 169.5, 170.3, 170.4 (3 CO amide). Anal. Calcd. for C47H64N6O8, 0.5H2O: C, 66.40; H, 7.70; N, 9.88. Found: C, 66.34; H, 7.67; N, 10.07.

Workup

  1. customThe crude residue was triturated with Et2O/pentane

Sources & evidence

ORD record
ord-8c7cb50a6d0e4f63994a4e2f2a4e5a6b
Source dataset
uspto-grants-2011_04
Patent number
US07919468B2

Reaction notes

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