Ammonia → Rilpivirine

HRID 2280429Notes

Reaction equation

HRID 2280429 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:14]([CH3:15])=[CH:13][C:12](/[CH:16]=[CH:17]/[C:18]#[N:19])=[CH:11][C:10]=2[CH3:20])[CH:5]=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.N>C(O)(C)C>[CH3:20][C:10]1[CH:11]=[C:12](/[CH:16]=[CH:17]/[C:18]#[N:19])[CH:13]=[C:14]([CH3:15])[C:9]=1[NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]#[N:27])=[CH:28][CH:29]=2)[N:7]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 133964-AminobenzonitrileHCID 72721606HCID 72721606, compound

Product 1

HCID 6451164RilpivirineYield 77.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
82.5 °C

Procedure

To a mixture of (E)-3-(4-(2-chloropyrimidin-4-ylamino)-3,5-dimethylphenyl)acrylonitrile (40 gm), 4-aminobenzonitrile (17 gm), isopropanol (400 ml) and p-toluenesulfonic acid (20 ml) were added at room temperature. The reaction mixture was then heated to 80 to 85° C. and stirred for 4 hours. The reaction mass was then cooled to 0° C. and pH was adjusted to 10 to 11 with aqueous ammonia solution. The separated solid was filtered and then dried to provide 40 gm of rilpivirine.

Workup

  1. additionwere added at room temperature
  2. temperatureThe reaction mass was then cooled to 0° C.
  3. filtrationThe separated solid was filtered
  4. customdried

Sources & evidence

ORD record
ord-2ae6918ee7b041b9abef86dac4a38581
Source dataset
uspto-grants-2015_09
Patent number
US09139535B2

Reaction notes

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