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

HRID 2074352Notes

Reaction equation

HRID 2074352 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:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[C@H:23]([C:39]([NH:41][C@H:42]([C:44](O)=[O:45])[CH3:43])=[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>CN(C=O)C>[NH:22]([C:47]([O:49][C:50]([CH3:51])([CH3:53])[CH3:52])=[O:48])[C@H:23]([C:39]([NH:41][C@H:42]([C:44]([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:45])[CH3:43])=[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 57611766N-Boc-Tyr(Bn)-Ala-OH

Product 1

HCID 16736957N-Boc-Tyr(Bn)-Ala-Trp-NHPhYield 31.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

compound SP303r2. To a solution of Trp-NHPh (202 mg, 0.723 mmol) in CH2C12/DMF (3 mL, 1/1) at 0° C. were successively added N-Boc-Tyr(Bn)-Ala-OH (320 mg, 0.723 mmol), EDC (153.6 mg, 0.8 mmol) and HOBt (108 mg, 0.8 mmol). The resulting mixture was allowed to warm up to room temperature overnight. The solvent was evaporated and the crude was triturated with water. After filtration, the solid was collected and purified by precipitation in CH2Cl2/MeOH to give a white amorphous solid (160.3 mg, 31%). 1H NMR (300 MHz, DMSO-d6) δ 1.22 (d, J=7 Hz, 3H, CH3), 1.28 (s, 9H, (CH3)3), 2.63 (m, 1H, CH2), 2.89 (m, 1H, CH2), 3.06 (dd, J=14.5 Hz, 7.5 Hz, 1H, CH2), 3.2 (dd, J=14.5 Hz, 6.1 Hz, 1H, CH2), 4.1 (m, 1H, CHα), 4.34 (m, 1H, CHα), 4.69 (m, 1H, CHα), 5.02 (s, 2H, CH2 (Bn)), 6.88 (d, J=8.5 Hz, 2 aromatic H Tyr), 6.94 (m, 2 aromatic H Trp), 7.03 (t, J=7.4 Hz, 2 aromatic H Trp), 7.16 (m, 3 aromatic H), 7.25-7.42 (m, 8H), 7.58 (m, 3H), 8.02 (d, J=7.2 Hz, 1H), 8.18 (d, J=7.6 Hz, 1H), 10 (s, 1H, NH), 10.8 (s, 1H, NH). 13C NMR (75 MHz, DMSO-d6) δ 18.2 (CH3), 27.7 (CH2 Trp), 28.1 ((CH3)3), 36.3 (CH2 Tyr), 48.1, 54.2, 55.7 (CHα Ala, Tyr, Trp), 69 (CH2 (Bn)), 78 (C(CH3)3), 109.5, 111.2, 114.2, 118.2, 118.4, 119.4, 120.8, 123.3, 123.5, 127.3, 127.5, 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, 171.5, 172.1 (3 CO amide). Anal. Calcd. for C41H45N5O6, 0.5H2O: C, 69.08; H, 6.5; N, 9.82. Found: C, 68.82; H, 6.34; N, 9.79.

Workup

  1. customat 0° C.
  2. customThe solvent was evaporated
  3. customthe crude was triturated with water
  4. filtrationAfter filtration
  5. customthe solid was collected
  6. custompurified by precipitation in CH2Cl2/MeOH

Sources & evidence

ORD record
ord-d46f5a021fa64e6abf162743e4237140
Source dataset
uspto-grants-2011_04
Patent number
US07919468B2

Reaction notes

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