Ammonium Hydroxide → 2-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-thiazole-5-carboxylic acid amide
Reaction equation
C[O:2][C:3]([C:5]1[S:9][C:8]([C:10]2[N:15]3[CH:16]=[CH:17][N:18]=[C:14]3[C:13]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[CH:22][CH:21]=3)=[N:12][CH:11]=2)=[N:7][CH:6]=1)=O.[NH4+:32].[OH-].[NH4+].[Cl-]>CO>[N:26]1([C:23]2[CH:22]=[CH:21][C:20]([NH:19][C:13]3[C:14]4[N:15]([CH:16]=[CH:17][N:18]=4)[C:10]([C:8]4[S:9][C:5]([C:3]([NH2:32])=[O:2])=[CH:6][N:7]=4)=[CH:11][N:12]=3)=[CH:25][CH:24]=2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 2-[8-(4-morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-thiazole-5-carboxylic acid methyl ester (90 mg, 0.21 mmol), 35% NH4OH (2.5 mL), and NH4Cl (0.2 g), in MeOH (12 mL) is heated at 85° C. in a stem tube for 48 hours. The mixture is concentrated in vacuo and purified by silica gel column chromatography eluting with 99:1 and 97:3 DCM:NH3 (7M in MeOH). Trituration with diethyl ether-MeOH gives the title compound (4.9 mg, 6%). LCMS: Rt 2.52 min (90%), m/z (ES+) 422 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 3.13 (4H, m), 3.79 (4H, m), 7.00 (2H, d), 7.75 (1H, br s), 7.81 (1H, s), 7.91 (2H, d), 8.25 (1H, s), 8.28 (1H, br s), 8.55 (1H, s), 9.08 (1H, s), 10.05 (1H, s).
Workup
- concentrationThe mixture is concentrated in vacuo
- custompurified by silica gel column chromatography
- washeluting with 99:1 and 97:3 DCM
Sources & evidence
- ORD record
- ord-906ab2436dcb484fad6939789cc119f3
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08173656B2
Reaction notes
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