4-Methylmorpholine → CCR1 antagonist 9

HRID 559646Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[N:14][CH:15]=[C:16]([C:17]([OH:19])=O)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.Cl.[CH3:21][S:22]([C:25]1[CH:30]=[C:29]([CH2:31][NH2:32])[CH:28]=[CH:27][N:26]=1)(=[O:24])=[O:23].CN1CCOCC1.CCCP(=O)=O>O.CN1C(=O)CCC1>[CH3:21][S:22]([C:25]1[CH:30]=[C:29]([CH2:31][NH:32][C:17]([C:16]2[C:11]3[CH:10]=[N:9][N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[C:12]=3[CH:13]=[N:14][CH:15]=2)=[O:19])[CH:28]=[CH:27][N:26]=1)(=[O:24])=[O:23]

Participants

Conditions

Temperature: 60 °C

Procedure

A 250 mL flask was charged with 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (10.0 g, 33.9 mmol, 87.2 wt. %, 1.0 eq), (2-(methylsulfonyl)pyridin-4-yl)methanamine hydrochloride (8.54 g, 37.3 mmol, 97.3 wt. %, 1.10 eq), NMP (30 mL) and finally N-methylmorpholine (18.6 mL, 169.5 mmol, 5.0 eq). To the slurry was charged propylphosphonic anhydride (23.97 mL, 40.68 mmol, 50 wt. % solution in EtOAc, 1.2 eq). The batch was then heated to 60° C. and held at this temperature for 1 hour. Water (80 mL) was charged, and the batch was cooled to ambient temperature and held for 1 hour. The batch was filtered, the solid washed with water, and then oven dried under vacuum to afford the title compound as a light yellow solid, 12.7 g, >99.5 area % purity by HPLC, 88% yield.

Workup

temperaturethe batch was cooled to ambient temperature
waitheld for 1 hour
filtrationThe batch was filtered
washthe solid washed with water
customoven dried under vacuum

Sources & evidence

ORD record: ord-2b7843e9e23b4a5fba1904933e7f53f9
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063065B2

Reaction notes

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