4-chloro-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-6-one → HCID 67265104, compound

HRID 1685201Notes

Reaction equation

HRID 1685201 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[C:9]2[CH2:16][C:15](=[O:17])[NH:14][C:10]=2[N:11]=[CH:12][N:13]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]=[C:27]([CH:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)[N:28]([C@@H:30]3[CH2:35][CH2:34][CH2:33][N:32]([CH3:36])[CH2:31]3)[CH:29]=2)=[CH:21][C:20]=1[C:43]([F:46])([F:45])[F:44]>O>[ClH:7].[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]=[C:27]([CH:37]3[CH2:38][CH2:39][N:40]([C:8]4[C:9]5[CH2:16][C:15](=[O:17])[NH:14][C:10]=5[N:11]=[CH:12][N:13]=4)[CH2:41][CH2:42]3)[N:28]([C@@H:30]3[CH2:35][CH2:34][CH2:33][N:32]([CH3:36])[CH2:31]3)[CH:29]=2)=[CH:21][C:20]=1[C:43]([F:46])([F:44])[F:45]

Participants

5

Reactant 3

HCID 120958704-chloro-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-6-oneHCID 23665647Potassium tert-butoxideHCID 67264988HCID 67264988, compound

Product 1

HCID 67265104HCID 67265104, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Combine potassium tert-butoxide (1.1 equiv; 321 μmol; 36.8 mg); IPrPd(acac)Cl (0.1 equiv; 29.2 μmol; 18.4 mg) and stir bar in 4 mL vial and purge with nitrogen for 10 min. Add anhydrous DME (2.5 mL) followed by 4-chloro-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one (1 equiv; 292 μmol; 50 mg); (R)-3-[4-(4-fluoro-3-trifluoromethyl-phenyl)-2-piperidin-4-yl-imidazol-1-yl]-1-methyl-piperidine (1.1 equiv; 321 μmol; 131.8 mg) and heat to 80° C. for 18 h. Dilute with 15 mL water, filter, and rinse with water. Dissolve purple solid in EA, wash with saturated sodium bicarbonate, brine, dry with anhydrous MgSO4, filter, evaporate and purify on 40 g silica gel with 2-10% MeOH/DCM to provide 99.6 mg (0.18 mmol; 63%) of the title compound as the free base. Dissolve in DCM, add 1 equiv 1M HCl in ether and evaporate to provide 101 mg of the title compound. MS (ES+): m/z=544 (M+H).

Workup

  1. custompurge with nitrogen for 10 min
  2. filtrationfilter
  3. washrinse with water
  4. dissolutionDissolve purple solid in EA
  5. washwash with saturated sodium bicarbonate, brine
  6. dry with materialdry with anhydrous MgSO4
  7. filtrationfilter
  8. customevaporate
  9. custompurify on 40 g silica gel with 2-10% MeOH/DCM

Sources & evidence

ORD record
ord-7ef4bc3d329a4c92b58be4c3bd988553
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

Loading…