Isobutanol → HCID 178428168, compound

HRID 931206Notes

Reaction equation

HRID 931206 reaction equation
[NH2:1][C:2]1[C:7]([NH:8][C:9]([C:11]2([N:14]3[CH:18]=[CH:17][C:16]([CH3:19])=[N: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.[NH2:33][C:34]1[C:39]([NH:40][C:41]([C:43]2([N:46]3[C:50]([CH3:51])=[CH:49][CH:48]=[N:47]3)[CH2:45][CH2:44]2)=O)=[CH:38][CH:37]=[C:36]([N:52]2[CH2:57][CH2:56][CH2:55][C@@H:54]([C:58]([N:60]3[CH2:64][CH2:63][CH2:62][CH2:61]3)=[O:59])[CH2:53]2)[N:35]=1.C[O-].[Na+].C(O)C(C)C>CO>[CH3:19][C:16]1[CH:17]=[CH:18][N: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)[N:15]=1.[CH3:51][C:50]1[N:46]([C:43]2([C:41]3[NH:33][C:34]4=[N:35][C:36]([N:52]5[CH2:57][CH2:56][CH2:55][C@@H:54]([C:58]([N:60]6[CH2:64][CH2:63][CH2:62][CH2:61]6)=[O:59])[CH2:53]5)=[CH:37][CH:38]=[C:39]4[N:40]=3)[CH2:45][CH2:44]2)[N:47]=[CH:48][CH:49]=1

Participants

7

Reactant 4

HCID 6560IsobutanolHCID 10942334Sodium MethoxideHCID 117966453(R)-N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(3-methyl-1H-pyrazol-1-yl)cyclopropanecarboxamideHCID 117966530(R)-N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(5-methyl-1H-pyrazol-1-yl)cyclopropanecarboxamide

Product 2

HCID 178428168HCID 178428168, compoundHCID 178428695HCID 178428695, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

Into a vial containing (R)—N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(3-methyl-1H-pyrazol-1-yl)cyclopropanecarboxamide or (R)—N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(5-methyl-1H-pyrazol-1-yl)cyclopropanecarboxamide (60 mg, 0.14 mmol) and sodium methoxide (25% wt in methanol, 118 μL) was added isobutanol (0.4 mL) and methanol (0.2 mL). The reaction mixture was heated to 110° C. for 5 h. The solvent was removed under reduced pressure and the residue was purified via HPLC to afford (R)-(1-(2-(1-(3-methyl-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone or (R)-(1-(2-(1-(5-methyl-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (Example 89, starting from Intermediate 10): MS (ESI+) (M+H) 420.3; HPLC retention time 1.85 min (Method A).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified via HPLC

Sources & evidence

ORD record
ord-6426710f5ea546dea26f8a24abf40e8c
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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