Methanol → HCID 178422493, compound

HRID 931204Notes

Reaction equation

HRID 931204 reaction equation
[NH2:1][C:2]1[C:7]([NH:8][C:9]([C:11]2([C:14]3[O:18][N:17]=[C:16]([CH3:19])[CH:15]=3)[CH2:13][CH2:12]2)=O)=[CH:6][CH:5]=[C:4]([N:20]2[CH2:25][CH2:24][CH2:23][C@@H:22]([C:26]([N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[O:27])[CH2:21]2)[N:3]=1.C[O-].[Na+].CO>C(O)C(C)C>[CH3:19][C:16]1[CH:15]=[C:14]([C:11]2([C:9]3[NH:1][C:2]4=[N:3][C:4]([N:20]5[CH2:25][CH2:24][CH2:23][C@@H:22]([C:26]([N:28]6[CH2:29][CH2:30][CH2:31][CH2:32]6)=[O:27])[CH2:21]5)=[CH:5][CH:6]=[C:7]4[N:8]=3)[CH2:12][CH2:13]2)[O:18][N:17]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 10942334Sodium Methoxide2×HCID 117966665(R)-N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridine-3-yl)-1-(3-methylisoxazol-5-yl)cyclopropanecarboxamide

Product 1

HCID 178422493HCID 178422493, compound

Reagents, catalysts & solvents 1

HCID 6560IsobutanolSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (R)—N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridine-3-yl)-1-(3-methylisoxazol-5-yl)cyclopropanecarboxamide (94 mg, 0.21 mmol) in isobutanol (2 mL) was added sodium methoxide (25% in methanol, 98 μL, 0.43 mmol) followed by methanol (0.9 mL). The reaction mixture was stirred at 110° C. for 18 h. An additional portion of sodium methoxide (25% in methanol, 98 μL, 0.43 mmol) was added and the reaction mixture was stirred at 110° C. for 3 h. The mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via HPLC to afford (R)-(1-(2-(1-(3-methylisoxazol-5-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone. MS (ESI+) (M+H) 421.2; HPLC retention time 2.02 min (Method A).

Workup

  1. stirringthe reaction mixture was stirred at 110° C. for 3 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washwashed with a saturated aqueous solution of sodium bicarbonate
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified via HPLC

Sources & evidence

ORD record
ord-b0dc691900bb4453956fdf291e6a1045
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

Loading…