Methanol → 5-cyclopropyl-2-[4-(4-fluorophenoxy)phenyl]-N-methyl-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamide

HRID 1037535Notes

Reaction equation

HRID 1037535 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([C:17]([NH:19][CH3:20])=[O:18])=[C:15]3[C:10]([CH:11]=[C:12]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[C:13]([CH:21]4[CH2:23][CH2:22]4)=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:35][C:36]1[CH:41]=[CH:40][C:39]([OH:42])=[CH:38][CH:37]=1.CO>N1C=CC=CC=1.[Cu]I.[Cu]>[CH:21]1([C:13]2[C:12]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:11][C:10]3[C:15](=[C:16]([C:17]([NH:19][CH3:20])=[O:18])[N:8]([C:5]4[CH:6]=[CH:7][C:2]([O:42][C:39]5[CH:40]=[CH:41][C:36]([F:35])=[CH:37][CH:38]=5)=[CH:3][CH:4]=4)[N:9]=3)[CH:14]=2)[CH2:23][CH2:22]1

Participants

8

Reactant 4

HCID 887MethanolHCID 97324-FluorophenolHCID 11430Potassium CarbonateHCID 56962687HCID 56962687, compound

Product 1

HCID 569626885-cyclopropyl-2-[4-(4-fluorophenoxy)phenyl]-N-methyl-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamideYield 17%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1049PyridineSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of Compound (1) (50 mg, 0.11 mmol), potassium carbonate (30 mg, 0.22 mmol), copper(I) iodide (10 mg, 0.05 mmol), copper (6.9 mg, 0.11 mmol) and 4-fluorophenol (18 mg, 0.16 mmol) in pyridine (1 mL) was heated to 150° C. for 16 h in a sealed-tube. After cooling to RT, MeOH (5 mL) was added and the mixture was filtered through celite and washed with more MeOH. The filtrate was concentrated in vacuo to give a crude mixture which was purified by reverse phase flash column chromatography eluting with ACN/water (10-100%) to give 5-cyclopropyl-2-[4-(4-fluorophenoxy)phenyl]-N-methyl-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamide (2) (9 mg, 17%) as a pale yellow solid. ESI-MS m/z calculated for [M+H]+: 495.15; found: 495.12.

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe mixture was filtered through celite
  3. washwashed with more MeOH
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto give a crude mixture which
  6. customwas purified by reverse phase flash column chromatography
  7. washeluting with ACN/water (10-100%)

Sources & evidence

ORD record
ord-5c45a61abedc441494a8e144753fafb9
Source dataset
uspto-grants-2013_10
Patent number
US08546389B2

Reaction notes

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