Sodium triacetoxyborohydride → N1-Methyl-5-(2-(((4-(azetidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide

HRID 2376914Notes

Reaction equation

HRID 2376914 reaction equation
Cl.[NH:2]1[CH2:5][CH2:4][CH2:3]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:20][NH:21][C:22]([N:24]1[C:32]2[C:27](=[CH:28][C:29]([O:33][C:34]3[CH:39]=[CH:38][N:37]=[C:36]([NH:40][C:41]([N:43]4[CH2:48][CH2:47][C:46](=O)[CH2:45][CH2:44]4)=[O:42])[CH:35]=3)=[CH:30][CH:31]=2)[CH:26]=[CH:25]1)=[O:23]>ClCCl>[CH3:20][NH:21][C:22]([N:24]1[C:32]2[C:27](=[CH:28][C:29]([O:33][C:34]3[CH:39]=[CH:38][N:37]=[C:36]([NH:40][C:41]([N:43]4[CH2:48][CH2:47][CH:46]([N:2]5[CH2:5][CH2:4][CH2:3]5)[CH2:45][CH2:44]4)=[O:42])[CH:35]=3)=[CH:30][CH:31]=2)[CH:26]=[CH:25]1)=[O:23]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 12308726Azetidine hydrochlorideHCID 59855857N1-Methyl-5-(2-(4-oxopiperidin-1-ylcarbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide

Product 1

HCID 21949261N1-Methyl-5-(2-(((4-(azetidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamideYield 0.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Azetidine hydrochloride (179 mg, 2.00 mmol) and sodium triacetoxyborohydride (434 mg, 2.05 mmol) were added to a dichloromethane (3.7 ml) solution of N1-methyl-5-(2-(4-oxopiperidin-1-ylcarbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide (555 mg, 1.36 mmol) synthesized in Example 40, and stirred overnight at room temperature. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was dried over anhydrous sodium sulfate. The solution was concentrated under reduced pressure; and the residue was purified by use of silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system). The resultant was washed with a solvent mixture of ether-hexane=1:1; and the solid was filtered off to yield crystals of the title compound (5 mg), and a mixture (410 mg) including the title compound.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. dry with materialand the organic layer was dried over anhydrous sodium sulfate
  3. concentrationThe solution was concentrated under reduced pressure
  4. customand the residue was purified by use of silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system)
  5. washThe resultant was washed with a solvent mixture of ether-hexane=1:1
  6. filtrationand the solid was filtered off

Sources & evidence

ORD record
ord-13db06454b704ead996f0d4578b88d20
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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