THF diethylamine → N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 74787Notes

Reaction equation

HRID 74787 reaction equation
C1C2C(COC([NH:18][C@H:19]([C:23]([N:25]([C@@H:27]([C@@H:57]([CH3:60])[CH2:58][CH3:59])[C@H:28]([O:55][CH3:56])[CH2:29][C:30]([N:32]3[CH2:36][CH2:35][CH2:34][C@H:33]3[C@H:37]([O:53][CH3:54])[C@@H:38]([CH3:52])[C:39]([NH:41][C@H:42]([CH3:51])[C@@H:43]([OH:50])[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:40])=[O:31])[CH3:26])=[O:24])[CH:20]([CH3:22])[CH3:21])=O)C3C(=CC=CC=3)C=2C=CC=1.C1COCC1.C(NCC)C>>[OH:50][C@@H:43]([C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[C@H:42]([NH:41][C:39](=[O:40])[C@H:38]([CH3:52])[C@H:37]([C@@H:33]1[CH2:34][CH2:35][CH2:36][N:32]1[C:30](=[O:31])[CH2:29][C@@H:28]([O:55][CH3:56])[C@@H:27]([N:25]([CH3:26])[C:23](=[O:24])[C@H:19]([CH:20]([CH3:21])[CH3:22])[NH2:18])[C@@H:57]([CH3:60])[CH2:58][CH3:59])[O:53][CH3:54])[CH3:51]

Participants

3

Reactant 2

HCID 19023656THF diethylamineHCID 89582415N~2~-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]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 89573130N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamideYield 43.2%

Procedure

To a stirring solution of #132 (1.33 g, 1.60 mmol, 1.0 eq) in 10 mL of THF diethylamine (5 mL, 50 mM, 31.3 eq) was added. The reaction was allowed to stir at room temperature for 4 hours. Reaction was concentrated in vacuo and the residue was purified by silica chromatography (Gradient: 0%-30% methanol in ethyl acetate) producing #133 (418 mg, 43%) as a white solid. LC-MS (Protocol Q1): m/z 605.2 [M+H+] retention time=1.48 minutes.

Workup

  1. customReaction
  2. concentrationwas concentrated in vacuo
  3. customthe residue was purified by silica chromatography (Gradient: 0%-30% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-1bdd3b53cc8848da973467386c9c0b65
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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