Diisopropylethylamine → 1-(tert-butoxycarbonyl)-2-methyl-L-prolyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 2282897Notes

Reaction equation

HRID 2282897 reaction equation
[CH:1]1([CH2:8][CH2:9][NH:10][C:11](=[O:42])[C@H:12]([CH3:41])[C@H:13]([C@@H:16]2[CH2:20][CH2:19][CH2:18][N:17]2[C:21](=[O:40])[CH2:22][C@@H:23]([O:38][CH3:39])[C@@H:24]([N:29]([CH3:37])[C:30](=[O:36])[C@H:31]([CH:33]([CH3:35])[CH3:34])[NH2:32])[C@@H:25]([CH3:28])[CH2:26][CH3:27])[O:14][CH3:15])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=[CH:2]1.[C:43]([O:47][C:48]([N:50]1[CH2:57][CH2:56][CH2:55][C@@:51]1([CH3:58])[C:52](O)=[O:53])=[O:49])([CH3:46])([CH3:45])[CH3:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>ClCCl>[C:43]([O:47][C:48]([N:50]1[CH2:57][CH2:56][CH2:55][C@@:51]1([CH3:58])[C:52]([NH:32][C@H:31]([C:30]([N:29]([C@@H:24]([C@@H:25]([CH3:28])[CH2:26][CH3:27])[C@H:23]([O:38][CH3:39])[CH2:22][C:21]([N:17]1[CH2:18][CH2:19][CH2:20][C@H:16]1[C@H:13]([O:14][CH3:15])[C@@H:12]([CH3:41])[C:11]([NH:10][CH2:9][CH2:8][CH:1]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=[CH:2]1)=[O:42])=[O:40])[CH3:37])=[O:36])[CH:33]([CH3:34])[CH3:35])=[O:53])=[O:49])([CH3:46])([CH3:44])[CH3:45]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11206950(2S)-1-(tert-Butoxycarbonyl)-2-methylpyrrolidine-2-carboxylic acidHCID 86685760N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Product 1

HCID 867627161-(tert-butoxycarbonyl)-2-methyl-L-prolyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

According to the general procedure D, from #176 (100 mg, 0.170 mmol, 1 eq.), (S)-1-(tert-butoxycarbonyl)-2-methyl-L-proline (50.7 mg, 0.221 mmol, 1.3 eq.), dichloromethane (4.3 mL), HATU (84.9 mg, 0.221 mmol, 1.3 eq.) and N,N-diisopropylethylamine (0.123 mL, 0.697 mmol, 4.1 eq.), was synthesized the crude desired material, which was purified by silica gel chromatography (Gradient: 0 to 100% ethyl acetate in heptane) to afford #181 (142 mg, assume quantitative yield). LC-MS (Protocol Q1): m/z 800.6 [M+H+], retention time=1.11 minutes.

Workup

  1. customwas purified by silica gel chromatography (Gradient: 0 to 100% ethyl acetate in heptane)
  2. customto afford #181 (142 mg, assume quantitative yield)

Sources & evidence

ORD record
ord-2b7f7257ce2b408b889104a457b49bfa
Source dataset
uspto-grants-2015_09
Patent number
US09138486B2

Reaction notes

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