Hydrochloric Acid → 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acid

HRID 627329Notes

Reaction equation

[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:25]=[CH:24][C:19]([C:20]([O:22]C)=[O:21])=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:26](=[O:30])[N:27]([CH3:29])[CH3:28])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-].Cl.[Li+].[Cl-]>CC(O)C.O>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:25]=[CH:24][C:19]([C:20]([OH:22])=[O:21])=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:26](=[O:30])[N:27]([CH3:28])[CH3:29])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of methyl 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinate (1.0 g, 2.4 mmol) in 2-propanol (60 mL) were added LiOH (0.29 g, 5.0 eq) and water (12 mL) and the resulting mixture was stirred at 60° C. for 1 h. After cooling to room temperature, the reaction mixture was treated with 1 N HCl (12.24 mL, 5 eq) and concentrated in vacuo which gave 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acid as a light yellow solid (1.40 g) in 95% yield as the LiCl (5 equiv) co-salt and was used for the next reaction without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.30 (br s, 1H), 11.24 (br s, 1H), 9.03 (s, 1H), 8.88 (d, J=2.2 Hz, 1H), 8.31 (dd, J=8.7, 2.2 Hz, 1H), 8.11 (d, J=8.7 Hz, 1H), 6.81 (s, 1H), 4.79 (m, 1H), 3.06 (s, 6H), 2.41 (m, 2H), 2.02 (m, 4H), 1.67 (m, 2H); MS m/z 395.4 (M+H)+.

Workup

temperatureAfter cooling to room temperature
concentrationconcentrated in vacuo which

Sources & evidence

ORD record: ord-d5f187f67c6a450c88e4ac5814d8c177
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309252B2

Reaction notes

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