Ammonia → HCID 118497136, compound

HRID 522098Notes

Reaction equation

C([O:8][C:9]1[CH:10]=[C:11]([N:15]2[C:19]([NH:20][C:21](=[O:36])[C:22]3[CH:27]=[C:26]([C:28]4[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=4)[CH:25]=[CH:24][C:23]=3[Cl:35])=[CH:18][C:17]([C:37](OCC)=[O:38])=[N:16]2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1.[NH3:42].B(Cl)(Cl)Cl>CO>[Cl:35][C:23]1[CH:24]=[CH:25][C:26]([C:28]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:27][C:22]=1[C:21]([NH:20][C:19]1[N:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([OH:8])[CH:10]=2)[N:16]=[C:17]([C:37]([NH2:42])=[O:38])[CH:18]=1)=[O:36]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of ethyl 1-(3-(benzyloxy)phenyl)-5-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-1H-pyrazole-3-carboxylate (Example 128, 220 mg, 0.385 mmol) in methanol (3 mL) was added 880 ammonia (7 mL) and the reaction was heated at 60° C. for 18 hours in a Reactivial™. The reaction was cooled, concentrated in vacuo and dissolved in DCM (5 mL). The solution was cooled to 0° C. and boron trichloride (1M in DCM, 3.41 mL, 3.41 mmol) was added dropwise. The reaction was stirred at room temperature for 30 minutes before being quenched by the addition of methanol (20 mL) and stirred for 18 hours. The reaction was concentrated in vacuo azeotroping with MeOH. The residue was purified using preparative HPLC followed by trituration with TBME to afford the title compound (12 mg, 6%).

Workup

temperatureThe reaction was cooled
concentrationconcentrated in vacuo
dissolutiondissolved in DCM (5 mL)
temperatureThe solution was cooled to 0° C.
custombefore being quenched by the addition of methanol (20 mL)
stirringstirred for 18 hours
concentrationThe reaction was concentrated in vacuo
customazeotroping with MeOH
customThe residue was purified

Sources & evidence

ORD record: ord-3b11e0a440ad43af991852418b0ec19c
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328096B2

Reaction notes

Loading…