Water → 6-(6-Chloro-pyrimidin-4-yloxy)-isoquinoline-1-carboxylic acid [5-tert-butyl-2-(4-methoxy-phenyl)-2H-pyrazol-3-yl]-amide

HRID 1094527Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15]([C:19](Cl)=[O:20])=[N:14][CH:13]=[CH:12]3)[CH:3]=1.N1C=CC=CC=1.[C:28]([C:32]1[CH:33]=[C:34]([NH2:45])[N:35]([C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=2)[N:36]=1)([CH3:31])([CH3:30])[CH3:29].O>C(Cl)Cl>[C:28]([C:32]1[CH:33]=[C:34]([NH:45][C:19]([C:15]2[C:16]3[C:11](=[CH:10][C:9]([O:8][C:4]4[CH:3]=[C:2]([Cl:1])[N:7]=[CH:6][N:5]=4)=[CH:18][CH:17]=3)[CH:12]=[CH:13][N:14]=2)=[O:20])[N:35]([C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=2)[N:36]=1)([CH3:31])([CH3:29])[CH3:30]

Participants

Conditions

Temperature: 0 °C

Procedure

454.6 mg (1.42 mMol) 6-(6-Chloropyrimidin-4-yloxy)-isoquinoline-1-carbonyl chloride is dissolved in 10 ml CH2Cl2 and cooled to 0° C. At this temperature 0.46 ml (5.9 mMol) pyridine are added followed by 418.0 mg (1.7 mMol) 5-tert-butyl-2-(4-methoxy-phenyl)-2H-pyrazol-3-ylamine (Step 19.1). The reaction mixture is then allowed to warm to rt and stirred at ambient temperature for 1 h. It is worked up by addition of H2O and CH2Cl2. The organic layer is separated washed with brine and dried. After evaporation of the solvents the crude product is purified by chromatography (combi-flash: 40 g column, hexanes/EtOAc, gradient 0-50% EtOAc) to give the title compound as a yellow solid: m.p.: 156° C.; MS.

Workup

temperatureto warm to rt
customThe organic layer is separated
washwashed with brine
customdried
customAfter evaporation of the solvents the crude product
customis purified by chromatography (combi-flash: 40 g column, hexanes/EtOAc, gradient 0-50% EtOAc)

Sources & evidence

ORD record: ord-b8ea4dd83ead4dfcb9277975ae7ea8bb
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08133886B2

Reaction notes

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