Hydrochloric Acid → GSK-1034702 hydrochloride

HRID 2061497Notes

Reaction equation

HRID 2061497 reaction equation
[F:1][C:2]1[C:10]2[NH:9][C:8](=[O:11])[N:7]([CH:12]3[CH2:17][CH2:16][N:15]([CH:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[C:4]([CH3:24])[CH:3]=1.[ClH:25].C(OCC)C>CO>[ClH:25].[F:1][C:2]1[C:10]2[NH:9][C:8](=[O:11])[N:7]([CH:12]3[CH2:17][CH2:16][N:15]([CH:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[C:4]([CH3:24])[CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 16038386Gsk 1034702

Product 1

HCID 68622535GSK-1034702 hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-Fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one free base (102.73 mmol, 34.25 g, 1 wt) was suspended in methanol (10 vol. 342 ml). HCl 1M in diethyl ether (154 ml, 1.5 eq.) was added dropwise in 20 min. The slurry was magnetically stirred at ambient temp. for 3 hours. The solvents were evaporated and the solid triturated in diethyl ether (14.5 vol., 500 ml) for 20 min. Diethyl ether was decanted and the white solid was dried under high acuum at 40° C. overnight. Residual MeOH (7% w/w by NMR) was found. The solid was dried under high vacuum overnight at 40° C. The solid was triturated in diethyl ether (14.5 vol, 500 ml), filtered and dried again in the oven at 40° C./high vacuum for 4 hours, then at 60° C. overnight then at 80° C. for two hours. 36.1 g, 95%.

Workup

  1. customThe solvents were evaporated
  2. customthe solid triturated in diethyl ether (14.5 vol., 500 ml) for 20 min
  3. customDiethyl ether was decanted
  4. customthe white solid was dried under high acuum at 40° C. overnight
  5. customThe solid was dried under high vacuum overnight at 40° C
  6. customThe solid was triturated in diethyl ether (14.5 vol, 500 ml)
  7. filtrationfiltered
  8. customdried again in the oven at 40° C./high vacuum for 4 hours
  9. waitat 60° C. overnight then at 80° C. for two hours

Sources & evidence

ORD record
ord-d37b24d9d94a4737b8d7da3859700b56
Source dataset
uspto-grants-2012_10
Patent number
US08283364B2

Reaction notes

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