Potassium Carbonate → 2-(4-bromophenyl)-5-cyclopropyl-6-[3-hydroxypropyl(methylsulfonyl)amino]-N-methyl-indazole-3-carboxamide

HRID 1037539Notes

Reaction equation

HRID 1037539 reaction equation
[Br:1][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+].Br[CH2:36][CH2:37][CH2:38][OH:39]>C(#N)C.CCOC(C)=O>[Br:1][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]([N:24]([CH2:36][CH2:37][CH2:38][OH:39])[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

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 123083-Bromo-1-propanolHCID 56962687HCID 56962687, compound

Product 1

HCID 569627692-(4-bromophenyl)-5-cyclopropyl-6-[3-hydroxypropyl(methylsulfonyl)amino]-N-methyl-indazole-3-carboxamideYield 50%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Compound (1) (50 mg, 0.11 mmol) in ACN (4 mL) was added potassium carbonate (30 mg, 0.22 mmol) followed by 3-bromo-1-propanol (38 μL, 0.32 mmol). The mixture was heated to 80° C. and stirred for 16 h at which time no starting material was observed. The mixture was cooled to RT, diluted with EtOAc (10 mL), washed with water (3 mL), brine (3 mL) and dried (MgSO4). The solvent was removed in vacuo to give the crude mixture which was purified by flash column chromatography eluting with EtOAc/hexane (5-100%) to give 2-(4-bromophenyl)-5-cyclopropyl-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide (4) (28 mg, 50%). ESI-MS m/z calculated for [M+H]+: 521.09/523.08; found: 521.03/523.03.

Workup

  1. temperatureThe mixture was cooled to RT
  2. washwashed with water (3 mL), brine (3 mL)
  3. dry with materialdried (MgSO4)
  4. customThe solvent was removed in vacuo
  5. customto give the crude mixture which
  6. customwas purified by flash column chromatography
  7. washeluting with EtOAc/hexane (5-100%)

Sources & evidence

ORD record
ord-0dfb1729211b465c87c01eaa884dd064
Source dataset
uspto-grants-2013_10
Patent number
US08546389B2

Reaction notes

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