Acetic Acid → N1-Methyl-5-(2-(((4-(morpholin-4-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide

HRID 2376913Notes

Reaction equation

HRID 2376913 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[CH3:25][NH:26][C:27]([N:29]1[C:37]2[C:32](=[CH:33][C:34]([O:38][C:39]3[CH:44]=[CH:43][N:42]=[C:41]([NH:45][C:46]([N:48]4[CH2:53][CH2:52][C:51](=O)[CH2:50][CH2:49]4)=[O:47])[CH:40]=3)=[CH:35][CH:36]=2)[CH:31]=[CH:30]1)=[O:28]>ClCCl>[CH3:25][NH:26][C:27]([N:29]1[C:37]2[C:32](=[CH:33][C:34]([O:38][C:39]3[CH:44]=[CH:43][N:42]=[C:41]([NH:45][C:46]([N:48]4[CH2:53][CH2:52][CH:51]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)[CH2:50][CH2:49]4)=[O:47])[CH:40]=3)=[CH:35][CH:36]=2)[CH:31]=[CH:30]1)=[O:28]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 59855857N1-Methyl-5-(2-(4-oxopiperidin-1-ylcarbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide

Product 1

HCID 21949231N1-Methyl-5-(2-(((4-(morpholin-4-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamideYield 19.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Morpholine (228 mg, 1.64 mmol), sodium triacetoxyborohydride (372 mg, 1.76 mmol), and acetic acid (0.134 ml, 2.34 mmol) were added to a dichloromethane (3.5 ml) solution of N1-methyl-5-(2-(4-oxopiperidin-1-ylcarbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide (476 mg) 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 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 the title compound (110 mg) as crystals.

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 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-6a72b28916ab43ccbe8e361eaa3b2711
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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