Sodium hydride → N-[2-(3-{2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetyl]methanesulfonamide

HRID 244400Notes

Reaction equation

HRID 244400 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]([C:21]1[C:29]2[C:24](=[N:25][CH:26]=[CH:27][CH:28]=2)[N:23]([CH2:30][C:31](O)=[O:32])[CH:22]=1)([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[N:9]=[CH:8]2)[OH:4].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:48][S:49]([NH2:52])(=[O:51])=[O:50].[H-].[Na+]>CN(C=O)C>[F:1][C:2]([F:34])([F:35])[C:3]([C:21]1[C:29]2[C:24](=[N:25][CH:26]=[CH:27][CH:28]=2)[N:23]([CH2:30][C:31]([NH:52][S:49]([CH3:48])(=[O:51])=[O:50])=[O:32])[CH:22]=1)([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=1)[N:9]=[CH:8]2)[OH:4]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 59437259(3-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetic acid

Product 1

HCID 24958729N-[2-(3-{2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetyl]methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 107 mg (0.22 mmol) of (3-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetic acid in 3 mL of DMF was added 108 mg (0.66 mmol) of N,N-carbonyldiimidazole. The mixture stirred for 5 minutes and then 63 mg (0.66 mmol) of methanesulfonamide was added. After 30 minutes, the reaction was monitored by LCMS indicating only starting material [MS m/z 485.29 (MH+)]. To the mixture was added sodium hydride and the mixture stirred for 1.5 hours. The mixture was monitored by LCMS indicating desired product [MS m/z 562.37 (MH+)]. TLC (ethyl acetate or methanol-dichloromethane) indicated a new product. The mixture was diluted with saturated aqueous ammonium chloride and extracted with five 10 mL portions of ethyl acetate. The combined organic layers were washed with two 7 mL portions of saturated aqueous ammonium chloride, two 7 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The oily residue was chromatographed on silica gel using dichloromethane to load the sample and then methanol-dichloromethane (1-10%) to afford some mixed factions and clean fractions. Fractions containing product were chromatographed on four prep. plate (1 mm, methanol-dichloromethane 15:85). The most polar band was recovered eluting from the silica gel with 20% methanol-dichloromethane. The material was triturated with ether-hexanes to afford 42 mg (33%) of the title compound as a tan solid. MS m/z 562.39 (MH+).

Workup

  1. waitAfter 30 minutes
  2. stirringthe mixture stirred for 1.5 hours

Sources & evidence

ORD record
ord-249cc37137be42b29ea7a07a06e8d3ed
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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