Methanol → HCID 56984306, compound

HRID 2393287Notes

Reaction equation

HRID 2393287 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:36])([CH2:30][N:31]1[CH:35]=[N:34][CH:33]=[N:32]1)[CH:10]([N:12]1[C:17](=[O:18])[C:16]2[S:19][C:20]([C:22]3[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=3)=[CH:21][C:15]=2[N:14]=[CH:13]1)[CH3:11].[CH3:37][OH:38]>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:36])([CH2:30][N:31]1[CH:35]=[N:34][CH:33]=[N:32]1)[C@H:10]([N:12]1[C:17](=[O:18])[C:16]2[S:19][C:20]([C:22]3[CH:29]=[CH:28][C:25]([C:26](=[NH:27])[O:38][CH3:37])=[CH:24][CH:23]=3)=[CH:21][C:15]=2[N:14]=[CH:13]1)[CH3:11]

Participants

4

Reactant 2

HCID 887MethanolHCID 10481231HCID 10481231, compound

Product 1

HCID 56984306HCID 56984306, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a cooled (0° C.) solution of (1R,2R)-(4-[3-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-6-yl]benzonitrile (1.03 g, 2.04 mmol) (obtained in example 32) in MeOH (25 mL) and CHCl3 (5 mL) was bubbled HCl gas until saturation. The reaction mixture was allowed to stand at 0° C. overnight, and was then concentrated and poured to aqueous K2CO3 solution. CHCl3 was added, the organic phase was separated and the aqueous phase was reextracted with CHCl3. The combined organic extracts were washed with water and brine, dried over Na2SO4, filtered and concentrated to give the title compound as a white solid (1.03 g, 94%): mp 194°-201° C.; 1H NMR (300 MHz, CDCl3) δ (TMS) 8.60 (s, 1H, N=CH--N), 7.78 (s, 1H, triazole), 7.77 (s, 4H, arom), 7.74 (s, 1H, triazole), 7.60 (s, 1H, thiophene), 7.49 (dt, Jd =6.4, Jt =8.8, 1H, arom), 6.9-6.7 (m, 2H, arom), 5.98 (q, J=7.3, 1H, MeCH), 5.56 (broad s, 1H, OH), 5.20 (d, J=14.2, 1H, CH(H)), 4.02 (d, J=14.2, 1H, CH(H)), 3.97 (s, 3H, OCH3),1.32 (d, J=7.3, 3H, CHMe).

Workup

  1. customwas bubbled HCl gas until saturation
  2. concentrationwas then concentrated
  3. additionpoured to aqueous K2CO3 solution
  4. additionCHCl3 was added
  5. customthe organic phase was separated
  6. washThe combined organic extracts were washed with water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-1e419806f27c4d27851d7e78668e317b
Source dataset
uspto-grants-1998_09
Patent number
US05807854

Reaction notes

Loading…