Sodium Methoxide → HCID 178520999, compound

HRID 931202Notes

Reaction equation

HRID 931202 reaction equation
[NH2:1][C:2]1[C:7]([NH:8][C:9]([C:11]2([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=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+]>C(O)C(C)C.CO>[N:16]1[CH:17]=[CH:18][CH:19]=[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[CH2:32][CH2:31][CH2:30][CH2:29]6)=[O:27])[CH2:21]5)=[CH:5][CH:6]=[C:7]4[N:8]=3)[CH2:13][CH2:12]2)[CH:15]=1

Participants

5

Reactant 2

HCID 10942334Sodium MethoxideHCID 117966400(R)-N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(pyridin-3-yl)cyclopropanecarboxamide

Product 1

HCID 178520999HCID 178520999, compoundYield 21.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6560IsobutanolSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (R)—N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(pyridin-3-yl)cyclopropanecarboxamide (35 mg, 0.081 mmol) in isobutanol (500 μL) was added sodium methoxide (18 mg, 0.335 mmol) in methanol (250 μL). The reaction mixture was shaken 110° C. for 18 h. The solvent was evaporated under a nitrogen stream. The residue was partitioned between water (0.5 mL) and ethyl acetate (1.5 mL×3). The combined organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified via HPLC to afford (R)-(1-(2-(1-(pyridin-3-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (7.2 mg). MS (ESI+) (M+H) 417.3; HPLC retention time 1.59 min (Method A).

Workup

  1. customThe solvent was evaporated under a nitrogen stream
  2. customThe residue was partitioned between water (0.5 mL) and ethyl acetate (1.5 mL×3)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified via HPLC

Sources & evidence

ORD record
ord-04c87a673930499991b5a6176cf3a787
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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