Ammonia → Vemurafenib

HRID 1747259Notes

Reaction equation

HRID 1747259 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:16]([C:17]([C:19]4[C:20]([F:33])=[C:21]([NH:26][S:27]([CH2:30][CH2:31][CH3:32])(=[O:29])=[O:28])[CH:22]=[CH:23][C:24]=4[F:25])=[O:18])=[CH:15][N:14](C(=O)C4C(Cl)=CC=CC=4Cl)[C:11]3=[N:12][CH:13]=2)=[CH:4][CH:3]=1.C1COCC1.N>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:16]([C:17]([C:19]4[C:20]([F:33])=[C:21]([NH:26][S:27]([CH2:30][CH2:31][CH3:32])(=[O:28])=[O:29])[CH:22]=[CH:23][C:24]=4[F:25])=[O:18])=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 8028TetrahydrofuranHCID 51001026N-(3-(5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide

Product 1

HCID 42611257VemurafenibYield 74%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Crude compound 9 and THF (6 L) were added to a 12 L round-bottom flask and stirred until the clear solution was obtained. A solution of ammonia in methanol (1.24 L; 7M) was added and stirred for 24 h at 28-35° C. The reaction mixture was concentrated to near dryness after with methanol was added and concentrated at 45-50° C. The separated solid was filtered and dried at 45-50° C. under vacuum to obtain crude compound 10 (601.7 g; Purity=≧95%; Yield=85.4%). Recrystallization of the crude in acetone/methanol (2:1) provided compound 10 in 74% yield with a purity of 98.5%. 1H NMR (DMSO-d6): δ (ppm) 9.78 (s, 1H), 8.72-8.73 (d, J=2.2 Hz, 1H), 8.65 (brs, 1H), 8.26 (s, 1H), 7.79-7.82 (d, J=8.5 Hz, 2H), 7.57-7.61 (m, 3H), 7.28-7.32 (t, J=8.3 Hz, 1H), 2.50-2.52 (m, 2H), 1.73-1.78 (m, 2H), and 0.96-0.98 (t, 3H). MS (ESI) [M+H+]+=490.1 and 492.1.

Workup

  1. customwas obtained
  2. stirringstirred for 24 h at 28-35° C
  3. concentrationThe reaction mixture was concentrated
  4. additionwas added
  5. concentrationconcentrated at 45-50° C
  6. filtrationThe separated solid was filtered
  7. customdried at 45-50° C. under vacuum
  8. customto obtain crude compound 10 (601.7 g; Purity=≧95%; Yield=85.4%)
  9. customRecrystallization of the crude in acetone/methanol (2:1)

Sources & evidence

ORD record
ord-d4b4d0f5471b420bad4e24b684456ead
Source dataset
uspto-grants-2015_10
Patent number
US09150570B2

Reaction notes

Loading…