Hydrochloric Acid → HCID 56927258, compound

HRID 510439Notes

Reaction equation

HRID 510439 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:23])[C:10]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:13]=3[CH3:22])=[C:6]2[N:5]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:3]=1.[CH3:30][OH:31].[OH-:32].[Na+].Cl>CN(C)C=O.O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].O>[CH3:23][C:9]1[C:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:13]=2[CH3:22])=[C:6]2[N:5]=[C:4]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:3]=[C:2]([C:30]([OH:32])=[O:31])[N:7]2[N:8]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 86724878HCID 86724878, compound

Product 1

HCID 56927258HCID 56927258, compoundYield 55.5%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalyst2×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 7-chloro-2-methyl-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-5-(4-morpholinyl)pyrazolo[1,5-a]pyrimidine (2.82 g, 6.64 mmol), prepared using the same procedure used to prepare Example 10, in N,N-Dimethylformamide (50 mL) and methanol (34.1 mL, 843 mmol) was added palladium(II) acetate (0.224 g, 0.996 mmol), DPPF (0.552 g, 0.996 mmol). The reaction mixture was purged with carbon monoxide for 5 min and then TEA (2.78 mL, 19.91 mmol) was added in. The reaction mixture was stirred at 70° C. under CO atmosphere for 6 h. Additional palladium(II) acetate (0.224 g, 0.996 mmol) and DPPF (0.552 g, 0.996 mmol) was added in. The reaction mixture was purged with carbon monoxide for 5 min and then TEA (2.78 mL, 19.91 mmol) was added in. The reaction mixture was stirred at 70° C. under CO atmosphere for 16 h. The reaction was filtered through Celite, and the filtrate was concentrated. The residue was dissolved in Tetrahydrofuran (THF) (100 mL). To the solution of residue in THF was added sodium hydroxide (5.31 mL, 26.6 mmol). The reaction mixture was stirred at rt for 2 h. Water (50 mL) was added in. The reaction was acidified with 5 N HCl, then extracted with DCM (500 mL×3), dried and concentrated. The crude was purified on a silica column (EtOAc/Hexane: 20˜60%) to give the product (1.6 g, 53%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.23 (s, 3H) 2.44 (s, 3H) 3.50-3.62 (m, 4H) 3.62-3.71 (m, 4H) 3.97 (s, 2H) 6.98 (s, 1H) 7.22-7.33 (m, 1H) 7.38 (d, J=7.58 Hz, 1H) 7.52 (d, 1H), 14.60 (b.s., 1H); LC/MS: MS (ES+) m/e 435.4 [M+H]+.

Workup

  1. customto prepare Example 10
  2. customThe reaction mixture was purged with carbon monoxide for 5 min
  3. customThe reaction mixture was purged with carbon monoxide for 5 min
  4. stirringThe reaction mixture was stirred at 70° C. under CO atmosphere for 16 h
  5. filtrationThe reaction was filtered through Celite
  6. concentrationthe filtrate was concentrated
  7. dissolutionThe residue was dissolved in Tetrahydrofuran (THF) (100 mL)
  8. stirringThe reaction mixture was stirred at rt for 2 h
  9. extractionextracted with DCM (500 mL×3)
  10. customdried
  11. concentrationconcentrated
  12. customThe crude was purified on a silica column (EtOAc/Hexane: 20˜60%)

Sources & evidence

ORD record
ord-8c9805785e2741fa93e70f2d015040d0
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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