2,2-Dimethyl-3-phenylpropanoyl chloride → HCID 178488237, compound

HRID 897966Notes

Reaction equation

HRID 897966 reaction equation
[CH3:1][C:2]([CH3:13])([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3](Cl)=[O:4].[NH2:14][C:15]1[C:20]([O:21][CH3:22])=[CH:19][C:18]([C:23]2[C:31]3[C:26](=[N:27][CH:28]=[N:29][C:30]=3[NH2:32])[N:25]([C@H:33]3[CH2:38][CH2:37][C@H:36]([N:39]4[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]4)[CH2:35][CH2:34]3)[N:24]=2)=[C:17]([F:46])[CH:16]=1>N1C=CC=CC=1>[NH2:32][C:30]1[N:29]=[CH:28][N:27]=[C:26]2[N:25]([C@H:33]3[CH2:38][CH2:37][C@H:36]([N:39]4[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]4)[CH2:35][CH2:34]3)[N:24]=[C:23]([C:18]3[C:17]([F:46])=[CH:16][C:15]([NH:14][C:3](=[O:4])[C:2]([CH3:13])([CH3:1])[CH2:6][C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)=[C:20]([O:21][CH3:22])[CH:19]=3)[C:31]=12

Participants

4

Reactant 2

HCID 133072292,2-Dimethyl-3-phenylpropanoyl chlorideHCID 178488236HCID 178488236, compound

Product 1

HCID 178488237HCID 178488237, compoundYield 20.3%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

2,2-Dimethyl-3-phenylpropanoyl chloride (52 mg, 0.264 mmol) was added to a solution of trans-3-(4-amino-2-fluoro-5-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (80 mg, 0.176 mmol) in pyridine (1.5 mL). After 5 hours, the solvent was evaporated and the residue was first purified by flash column chromatography chromatography using dichloromethane/methanol (95:5 to 85:15) as mobile phase then by preparatory LC/MS to give trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-5-fluoro-2-methoxyphenyl)-2,2-dimethyl-3-phenylpropanamide (22 mg, 19%). 1H NMR (CDCl3-d) δ 1.33 (s, 6H), 1.57 (m, 2H), 1.92 (m, 2H), 2.15 (m, 6H), 2.30 (s, 3H), 2.49 (m, 4H), 2.66 (m, 3H), 2.95 (s, 2H), 3.84 (s, 3H), 4.76 (m, 1H), 5.51 (bs, 2H), 6.98 (d, J=6.86 Hz, 1H), 7.15 (m, 2H), 7.23 (m, 3H), 8.01 (s, 1H), 8.35 (s, 1H), 8.47 (d, J=11.88, 1H). LCMS LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=615.3, Rt=2.18 min.

Workup

  1. customthe solvent was evaporated
  2. customthe residue was first purified by flash column chromatography chromatography

Sources & evidence

ORD record
ord-ed888a28b8f140f18626f2ed43f40415
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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