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2-Pyrrolidone → 1-Benzyl-N-(3,4-difluorobenzyl)-6-(3,4-dihydro-2H-pyrrol-5-ylamino)-5-fluoro-2-isopropyl-1H-indole-3-carboxamide

HRID 40149
Notes
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Reaction equation

HRID 40149 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=O.O=P(Cl)(Cl)Cl.[NH2:12][C:13]1[CH:21]=[C:20]2[C:16]([C:17]([C:32]([NH:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([F:42])=[C:38]([F:43])[CH:37]=3)=[O:33])=[C:18]([CH:29]([CH3:31])[CH3:30])[N:19]2[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:15][C:14]=1[F:44]>C1(C)C=CC=CC=1.CCOC(C)=O>[CH2:22]([N:19]1[C:20]2[C:16](=[CH:15][C:14]([F:44])=[C:13]([NH:12][C:2]3[CH2:3][CH2:4][CH2:5][N:1]=3)[CH:21]=2)[C:17]([C:32]([NH:34][CH2:35][C:36]2[CH:41]=[CH:40][C:39]([F:42])=[C:38]([F:43])[CH:37]=2)=[O:33])=[C:18]1[CH:29]([CH3:30])[CH3:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 120252-PyrrolidoneHCID 24813Phosphorus oxychlorideHCID 597624006-amino-1-benzyl-N-(3,4-difluorobenzyl)-5-fluoro-2-isopropyl-1H-indole-3-carboxamide2×

Product 1

HCID 597624361-Benzyl-N-(3,4-difluorobenzyl)-6-(3,4-dihydro-2H-pyrrol-5-ylamino)-5-fluoro-2-isopropyl-1H-indole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 1140
Toluene
Solvent
HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-pyrrolidinone (47 mg, 0.55 mmol) and POCl3 (0.10 ml, 1.1 mmol) was stirred at 0° C. to room temperature for 2h. To the above mixture was then added a solution of 6-amino-1-benzyl-N-(3,4-difluorobenzyl)-5-fluoro-2-isopropyl-1H-indole-3-carboxamide (Compound 172, 50 mg, 0.11 mmol) in toluene (3 ml). The reaction was heated to 110° C. for 16 h and was cooled to room temperature, diluted with EtOAc, washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by reverse phase chromatography on C18 bonded silica gel (MeOH) to yield the title compound as a white solid.

Workup

  1. temperaturewas cooled to room temperature
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by reverse phase chromatography on C18 bonded silica gel (MeOH)

Sources & evidence

ORD record
ord-87efb787dd884b16baaff4567165b540
Source dataset
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08524917B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes