1-Hydroxybenzotriazole → ((S)-5-tert-butoxycarbonylamino-6-{(S)-2-[5-(4-fluoro-benzoyl)-pyridin-3-yl]-pyrrolidin-1-yl}-6-oxo-hexyl)-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 2093307Notes

Reaction equation

HRID 2093307 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([C@@H:16]3[CH2:20][CH2:19][CH2:18][NH:17]3)[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[C:21]([O:25][C:26]([NH:28][C@@H:29]([CH2:33][CH2:34][CH2:35][CH2:36][NH:37][C:38]([O:40][CH2:41][CH:42]1[C:54]2[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=2[C:48]2[C:43]1=[CH:44][CH:45]=[CH:46][CH:47]=2)=[O:39])[C:30](O)=[O:31])=[O:27])([CH3:24])([CH3:23])[CH3:22].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:44]1[C:43]2[CH:42]([CH2:41][O:40][C:38](=[O:39])[NH:37][CH2:36][CH2:35][CH2:34][CH2:33][C@H:29]([NH:28][C:26]([O:25][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:27])[C:30]([N:17]3[CH2:18][CH2:19][CH2:20][C@H:16]3[C:14]3[CH:13]=[N:12][CH:11]=[C:10]([C:8](=[O:9])[C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[CH:15]=3)=[O:31])[C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[C:48]=2[CH:47]=[CH:46][CH:45]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10983524(2S)-2-(((tert-butoxy)carbonyl)amino)-6-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)hexanoic acidHCID 58191781(4-fluoro-phenyl)-((S)-5-pyrrolidin-2-yl-pyridin-3-yl)-methanone

Product 1

HCID 58402903((S)-5-tert-butoxycarbonylamino-6-{(S)-2-[5-(4-fluoro-benzoyl)-pyridin-3-yl]-pyrrolidin-1-yl}-6-oxo-hexyl)-carbamic acid 9H-fluoren-9-ylmethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (4-fluoro-phenyl)-((S)-5-pyrrolidin-2-yl-pyridin-3-yl)-methanone (1.0 g, 3.7 mmol), (S)-2-tert-butoxycarbonylamino-6-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid (2.0 g, 4.4 mmol) and ethyldiisopropylamine (3 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 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 ((S)-5-tert-butoxycarbonylamino-6-{(S)-2-[5-(4-fluoro-benzoyl)-pyridin-3-yl]pyrrolidin-1-yl}-6-oxo-hexyl)-carbamic acid 9H-fluoren-9-ylmethyl ester as a light 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-92c59047964a425d8551ae6e162bc93d
Source dataset
uspto-grants-2013_05
Patent number
US08445440B2

Reaction notes

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