Sodium Hydroxide → Etravirine

HRID 1908951Notes

Reaction equation

HRID 1908951 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)[N:5]=[C:4]([O:17][C:18]2[C:25]([CH3:26])=[CH:24][C:21]([C:22]#[N:23])=[CH:20][C:19]=2[CH3:27])[CH:3]=1.[Br:28]Br.[OH-].[Na+].S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>ClCCl.O>[CH3:27][C:19]1[CH:20]=[C:21]([C:22]#[N:23])[CH:24]=[C:25]([CH3:26])[C:18]=1[O:17][C:4]1[N:5]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)[N:7]=[C:2]([NH2:1])[C:3]=1[Br:28]

Participants

7

Reactant 4

HCID 14798Sodium Hydroxide2×HCID 24408BromineHCID 486367GE-0012HCID 656671Sodium Pyrosulfite

Product 1

HCID 193962Etravirine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

4-[[6-amino-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl-benzonitrile (10 gm) was dissolved in dichloromethane (100 ml) at 0 to 5° C. and then added bromine solution (4.7 gm in 50 ml of dichloromethane). The reaction mass was stirred for 4 hours at 0 to 5° C. and then added water (100 ml). The pH of the reaction mass was adjusted to 9 to 10 with sodium hydroxide solution (4N, 10 ml). Sodium metabisulphite solution (0.5 gm in 2 ml of water) was added to the reaction mass and pH of the reaction mass was maintained between 7.5 to 8.5 with sodium hydroxide solution (4N, 10 ml). The separated solid was filtered and dried at 50 to 55° C. to obtain crude etravirine.

Workup

  1. filtrationThe separated solid was filtered
  2. customdried at 50 to 55° C.

Sources & evidence

ORD record
ord-0570b7ff909a4a92a87a468a8e674241
Source dataset
uspto-grants-2013_12
Patent number
US08598341B2

Reaction notes

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