1-Hydroxybenzotriazole → HCID 58402917, compound

HRID 2093311Notes

Reaction equation

HRID 2093311 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:49])[NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C@H:25]([NH2:48])[C:26]([N:28]4[CH2:32][CH2:31][CH2:30][C@H:29]4[C:33]4[CH:34]=[N:35][CH:36]=[C:37]([C:39](=[O:47])[C:40]5[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=5)[CH:38]=4)=[O:27])=[CH:20][CH:19]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:50]([O:54][C:55]([N:57]([CH3:63])[C@@H:58]([CH3:62])[C:59](O)=[O:60])=[O:56])([CH3:53])([CH3:52])[CH3:51].C(N(C(C)C)C(C)C)C.N1(O)C2C=CC=CC=2N=N1>CN(C=O)C.C(OCC)(=O)C>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:49])[NH:17][C:18]3[CH:19]=[CH:20][C:21]([CH2:24][C@H:25]([NH:48][C:59](=[O:60])[C@@H:58]([N:57]([C:55]([O:54][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:56])[CH3:63])[CH3:62])[C:26]([N:28]4[CH2:32][CH2:31][CH2:30][C@H:29]4[C:33]4[CH:34]=[N:35][CH:36]=[C:37]([C:39](=[O:47])[C:40]5[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=5)[CH:38]=4)=[O:27])=[CH:22][CH:23]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 67339703HCID 67339703, compound

Product 1

HCID 58402917HCID 58402917, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [4-((S)-2-amino-3-{(S)-2-[5-(4-fluoro-benzoyl)-pyridin-3-yl]-pyrrolidin-1-yl}-3-oxo-propyl)-phenyl]-carbamic acid 9H-fluoren-9-ylmethyl ester (I-2b: 2.4 g, 3.7 mmol), (S)-2-(tert-butoxycarbonyl-methyl-amino)-propionic acid (0.89 g, 4.4 mmol) and ethyldiisopropylamine (7 mL) in DMF (20 mL) was added a solution of 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (1.67 g, 4.4 mmol) and 1H-benzo[d][1,2,3]triazol-1-ol (0.6 g, 4.4 mmol) in DMF (10 mL) and the reaction mixture was shaken for 16 hours. The reaction mixture was diluted with ethyl acetate (300 mL), washed sequentially with brine (2×) (300 mL), saturated aqueous bicarbonate solution (300 mL), brine (300 mL), water (300 mL), and brine (300 mL), then dried over Na2SO4/MgSO4, and concentrated in vacuo to provide crude [4-((S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-{(S)-2-[5-(4-fluoro-benzoyl)-pyridin-3-yl]-pyrrolidin-1-yl}-3-oxo-propyl)-phenyl]-carbamic acid 9H-fluoren-9-ylmethyl ester as a yellow foam.

Workup

  1. washwashed sequentially with brine (2×) (300 mL), saturated aqueous bicarbonate solution (300 mL), brine (300 mL), water (300 mL), and brine (300 mL)
  2. dry with materialdried over Na2SO4/MgSO4
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1c3659a3fdff45e7bc90ea2d06e606e4
Source dataset
uspto-grants-2013_05
Patent number
US08445440B2

Reaction notes

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