Diisopropylethylamine → 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~2~-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methyl-L-valinamide

HRID 74802Notes

Reaction equation

HRID 74802 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:23]([N:25]([CH3:49])[C@@H:26]([C@@H:45]([CH3:48])[CH2:46][CH3:47])[C@H:27]([O:43][CH3:44])[CH2:28][C:29](OC3C(F)=C(F)C(F)=C(F)C=3F)=[O:30])=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.[CH:51]1([CH2:58][CH2:59][NH:60][C:61](=[O:72])[C@H:62]([CH3:71])[C@@H:63]([O:69][CH3:70])[C@@H:64]2[CH2:68][CH2:67][CH2:66][NH:65]2)[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=[CH:52]1.C(N(CC)C(C)C)(C)C>ClCCl>[CH:51]1([CH2:58][CH2:59][NH:60][C:61](=[O:72])[C@H:62]([CH3:71])[C@H:63]([C@@H:64]2[CH2:68][CH2:67][CH2:66][N:65]2[C:29](=[O:30])[CH2:28][C@@H:27]([O:43][CH3:44])[C@@H:26]([N:25]([CH3:49])[C:23](=[O:24])[C@H:19]([CH:20]([CH3:22])[CH3:21])[NH:18][C:16]([O:15][CH2:14][CH:12]2[C:13]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[C:6]3[C:11]2=[CH:10][CH:9]=[CH:8][CH:7]=3)=[O:17])[C@@H:45]([CH3:48])[CH2:46][CH3:47])[O:69][CH3:70])[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=[CH:57]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86685758pentafluorophenyl (3R,4S,5S)-4-[{N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl}(methyl)amino]-3-methoxy-5-methylheptanoateHCID 131731851(2R,3R)-N-[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanamide, hydrochloride salt

Product 1

HCID 89582252N-[(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~2~-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methyl-L-valinamideYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of #174 (706 mg, 1.02 mmol, 1 eq.) and #64 (311 mg, 1.02 mmol, 1 eq.) in dichloromethane (3 mL) was added N,N-diisopropylethylamine (400 mg, 3.07 mmol, 3 eq.). After 18 hours of stirring at room temperature, the reaction was concentrated in vacuo and purified by silica gel chromatography (Gradient: 0 to 100% ethyl acetate in heptane) to afford #175 (560 mg, 68%) as a white solid. LC-MS (Protocol Q1): m/z 611.8 [M+H+], retention time=1.15 minutes.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. custompurified by silica gel chromatography (Gradient: 0 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-06fa3ee9370e48f79d1f6768a3ba0fd5
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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