3-Chloropropionyl chloride → (R)-1-[3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-chloropropan-1-one

HRID 1471823Notes

Reaction equation

[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[N:16]([C@@H:24]3[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]3)[N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:30][CH2:31][CH2:32][C:33](Cl)=[O:34]>C1COCC1.C(OCC)(=O)C>[NH2:23][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:16]([C@@H:24]3[CH2:29][CH2:28][CH2:27][N:26]([C:33](=[O:34])[CH2:32][CH2:31][Cl:30])[CH2:25]3)[N:15]=[C:14]([C:11]3[CH:10]=[CH:9][C:8]([O:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:13][CH:12]=3)[C:22]=12

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (6) (0.40 g, 1.04 mmol) and TEA (0.29 mL, 2.08 mmol) in THF (15 mL) cooled to 0° C. was added 3-chloropropanoyl chloride (0.132 g, 2.08 mmol). After stirring 1 hr at 0° C., the reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (50 mL). The organic layer was dried (MgSO4), filtered and concentrated to collect 0.49 g of a white solid. The white solid was subjected to flash chromatography (5% MeOH/EtOAc) to provide 0.31 g (62%) of (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-3-chloropropan-1-one (9) as a white solid. 1H NMR (300 MHz, DMSO) δ 8.25 (s, 1H), 7.64 (d, 2H, J=8.5 Hz), 7.40 (m, 2H), 7.20-7.00 (m, 7H), 4.60 (m, 1H), 4.12-3.10 (m, 6H), 2.94-1.60 (m, 6H).

Workup

washwashed with water (50 mL)
dry with materialThe organic layer was dried (MgSO4)
filtrationfiltered
concentrationconcentrated
customto collect 0.49 g of a white solid

Sources & evidence

ORD record: ord-9ea462f41fd54e51b12243ffd5f41ebf
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012463B2

Reaction notes

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