Potassium Phosphate, Tribasic → 5-cyclopropyl-2-(4-cyclopropylphenyl)-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide

HRID 1037543Notes

Reaction equation

HRID 1037543 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]([N:24]([CH2:29][CH2:30][CH2:31][OH:32])[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.[CH:33]1(B(O)O)[CH2:35][CH2:34]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:21]1([C:13]2[C:12]([N:24]([CH2:29][CH2:30][CH2:31][OH:32])[S:25]([CH3:28])(=[O:26])=[O:27])=[CH:11][C:10]3[C:15](=[C:16]([C:17]([NH:19][CH3:20])=[O:18])[N:8]([C:5]4[CH:4]=[CH:3][C:2]([CH:33]5[CH2:35][CH2:34]5)=[CH:7][CH:6]=4)[N:9]=3)[CH:14]=2)[CH2:23][CH2:22]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 569627692-(4-bromophenyl)-5-cyclopropyl-6-[3-hydroxypropyl(methylsulfonyl)amino]-N-methyl-indazole-3-carboxamide

Product 1

HCID 675128685-cyclopropyl-2-(4-cyclopropylphenyl)-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamideYield 27.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed mixture of 2-(4-bromophenyl)-5-cyclopropyl-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide (10 mg, 0.019 mmol), cyclopropylboronic acid (5 mg, 0.058 mmol), potassium phosphate (17 mg, 0.080 mmol) in toluene (0.5 mL) and water (50 μL) were added tricyclohexylphosphine (1 mg, 0.0038 mmol) and Pd(OAc)2 (0.4 mg, 0.0019 mmol) and the reaction was heated at 100° C. for 2 h. The mixture was concentrated to dryness and purified by preparative LCMS (5-40-100% ACN in 0.1 aqueous formic acid) to afford Compound (53) as a white solid (2.5 mg, 27%). ESI-MS m/z calculated for [M+H]+: 483.2; found: 483.2; 1H NMR (400 MHz, MeOD) δ 7.85 (s, 1H), 7.58-7.43 (m, 2H), 7.39 (s, 1H), 7.28 (d, J=8.5 Hz, 2H), 4.06-3.81 (m, 2H), 3.76-3.57 (m, 2H), 3.17 (s, 3H), 2.94 (s, 3H), 2.54-2.34 (m, 1H), 2.19-1.96 (m, 1H), 1.96-1.68 (m, 2H), 1.21-0.94 (m, 5H), 0.85-0.76 (m, 2H), 0.75-0.59 (m, 1H).

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. custompurified by preparative LCMS (5-40-100% ACN in 0.1 aqueous formic acid)

Sources & evidence

ORD record
ord-6fc317b78fec4584bcec91c906a7a3b8
Source dataset
uspto-grants-2013_10
Patent number
US08546389B2

Reaction notes

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