Benzylamine → ((3S,5S)-5-benzylcarbamoyl-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-pyrrolidin-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 1481922Notes

Reaction equation

HRID 1481922 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:49])[C@@H:9]([CH3:48])[C:10]([NH:12][C@@H:13]([CH:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1)[C:14]([N:16]1[CH2:20][C@@H:19]([NH:21][C:22]([O:24][CH2:25][CH:26]2[C:38]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[C:32]3[C:27]2=[CH:28][CH:29]=[CH:30][CH:31]=3)=[O:23])[CH2:18][C@H:17]1[C:39]([OH:41])=O)=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:83]([NH2:90])[C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1>CN(C=O)C>[CH:28]1[C:27]2[CH:26]([CH2:25][O:24][C:22](=[O:23])[NH:21][C@H:19]3[CH2:18][C@@H:17]([C:39](=[O:41])[NH:90][CH2:83][C:84]4[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=4)[N:16]([C:14](=[O:15])[C@@H:13]([NH:12][C:10](=[O:11])[C@@H:9]([N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:49])[CH3:48])[CH:42]4[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]4)[CH2:20]3)[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]=2[CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90231415(2S,4S)-1-{(S)-2-[(S)-2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid2×

Product 1

HCID 118677385((3S,5S)-5-benzylcarbamoyl-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-pyrrolidin-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To (2S,4S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid (Intermediate 27) in DMF at 0° C. was added DIPEA (116 μL, 0.66 mmol) and HATU (93 mg, 0.24 mmol). The mixture was stirred at 0° C. for 15 minutes and then benzylamine (26.1 mg, 0.24 mmol) in DMF (0.5 mL) was added dropwise, the cooling bath removed and the reaction stirred for 2 h. The mixture was diluted with water and extracted with EtOAc. The combined extracts were washed with saturated ammonium chloride solution, saturated sodium bicarbonate solution, water, and brine and dried over anhydrous magnesium sulfate. Concentration gave ((3S,5S)-5-benzylcarbamoyl-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-pyrrolidin-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester as a foam which was used without purification.

Workup

  1. customthe cooling bath removed
  2. stirringthe reaction stirred for 2 h
  3. additionThe mixture was diluted with water
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with saturated ammonium chloride solution, saturated sodium bicarbonate solution, water, and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationConcentration

Sources & evidence

ORD record
ord-e3305fbd75eb47ce98422b6277e19fbe
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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