Hydrochloric Acid → 6-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-methyl-3-pyridin-2-yl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine

HRID 2177594Notes

Reaction equation

HRID 2177594 reaction equation
[CH3:1][N:2]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)=[C:9]2[C:4]([CH2:5][N:6]([C:17]([O:19]C(C)(C)C)=O)[CH2:7][CH2:8]2)=[N:3]1.Cl.O1CCOCC1.[Cl:31][C:32]1[C:40]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:38]=[CH:37][C:33]=1C(O)=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl.CO>[Cl:31][C:32]1[C:40]([C:41]([F:42])([F:43])[F:44])=[CH:39][CH:38]=[CH:37][C:33]=1[C:17]([N:6]1[CH2:7][CH2:8][C:9]2=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)[N:2]([CH3:1])[N:3]=[C:4]2[CH2:5]1)=[O:19]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27366772-Chloro-3-(trifluoromethyl)benzoic acidHCID 90408677HCID 90408677, compound

Product 1

HCID 904086386-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-methyl-3-pyridin-2-yl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 2-methyl-3-(pyridin-2-yl)-4,5-dihydro-2H-pyrazolo[3,4-c]pyridine-6(7H)-carboxylate (135 mg, 0.429 mmol) in CH2Cl2 (5 mL) was added 4 M HCl in dioxane (0.43 mL, 1.72 mmol). The reaction was allowed to stir at rt for 1 h, then 1 mL MeOH was added and the reaction was stirred overnight. The reaction was concentrated to a yellow gum. It was combined with 2-chloro-3-(trifluoromethyl)benzoic acid (155 mg, 0.690 mmol), BOP (305 mg, 0.690 mmol) and triethylamine (0.37 mL, 2.65 mmol). After stirring overnight at rt, the reaction was filtered and purified by HPLC (Agilent prep system, Waters XBridge C18 5 μm 50×100 mm column, 5-99% MeOH/20 nM NH4OH over 18 min at 80 mL/min). The desired product was isolated as a white solid (56 mg, 31%).

Workup

  1. stirringthe reaction was stirred overnight
  2. concentrationThe reaction was concentrated to a yellow gum
  3. stirringAfter stirring overnight at rt
  4. filtrationthe reaction was filtered
  5. custompurified by HPLC (Agilent prep system, Waters XBridge C18 5 μm 50×100 mm column, 5-99% MeOH/20 nM NH4OH over 18 min at 80 mL/min)

Sources & evidence

ORD record
ord-6376bcfce1cc417ea70ae22967bb6aae
Source dataset
uspto-grants-2015_06
Patent number
US09066946B2

Reaction notes

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