Sodium Carbonate → Rilpivirine

HRID 1847136Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[N:3]=1.Cl.[CH3:18][C:19]1[CH:24]=[C:23]([CH:25]=[CH:26][C:27]#[N:28])[CH:22]=[C:21]([CH3:29])[C:20]=1[NH2:30].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[CH3:18][C:19]1[CH:24]=[C:23](/[CH:25]=[CH:26]/[C:27]#[N:28])[CH:22]=[C:21]([CH3:29])[C:20]=1[NH:30][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[N:3]=1

Participants

Conditions

Temperature: 87.5 °C

Procedure

4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile (100 gms) and 2,6-dimethyl-4-(2-cyanoethenyl) phenylamine hydrochloride (90.65 gms) were mixed with acetonitrile (800 ml) in an inert atmosphere and heated at 85-90° C. till completion of the reaction, as monitored by HPLC. The reaction mixture was cooled to 40° C. and pH of the reaction mass was adjusted to ≈ pH 10 with 20% sodium carbonate solution. The reaction mass was filtered at 5 to 10° C. and dried to yield Rilpivirine (110 gms). Rilpivirine thus obtained was dissolved in acetone (3600 ml) and after optional charcoal treatment was concentrated to 500 ml and was filtered at 5-10° C., dried to give Rilpivirine (80 gms), which was then added to dimethyl sulfoxide (338 ml) and heated to 70-75° C. The mixture was cooled to 50 to 55° C. and mixed with hydrochloric acid (25 ml) with constant stirring. Water (1350 ml) was added to the mixture at 40 to 45° C., which was stirred and cooled further. The reaction mass was filtered at 25 to 30° C. and the wet cake was dried to give 90 gms of Rilpivirine hydrochloride (I) having Z isomer less than 0.1%.

Workup

temperatureThe reaction mixture was cooled to 40° C.
filtrationThe reaction mass was filtered at 5 to 10° C.
customdried

Sources & evidence

ORD record: ord-d65342b354fd487eb26de670dd5cf1ac
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952155B2

Reaction notes

Loading…