Cyclobutanone → 6-[(3-Cyclobutyl-8-Iodo-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide

HRID 222725Notes

Reaction equation

HRID 222725 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:11][C:12]2[C:22]([I:23])=[CH:21][C:15]3[CH2:16][CH2:17][NH:18][CH2:19][CH2:20][C:14]=3[CH:13]=2)=[CH:9][CH:10]=1)=[O:4].[C:24]1(=O)[CH2:27][CH2:26][CH2:25]1>C(O)(=O)C.CO>[CH:24]1([N:18]2[CH2:17][CH2:16][C:15]3[CH:21]=[C:22]([I:23])[C:12]([O:11][C:8]4[N:7]=[CH:6][C:5]([C:3]([NH:2][CH3:1])=[O:4])=[CH:10][CH:9]=4)=[CH:13][C:14]=3[CH2:20][CH2:19]2)[CH2:27][CH2:26][CH2:25]1

Participants

5

Reactant 2

HCID 14496CyclobutanoneHCID 57440290N-Methyl-6-(8-Iodo-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yloxy)-3-pyridinecarboxamide

Product 1

HCID 100279976-[(3-Cyclobutyl-8-Iodo-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

N-Methyl-6-(8-iodo-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yloxy)-3-pyridinecarboxamide (D43) (423 mg, 1.0 mmol) was dissolved in 2.5% acetic acid in methanol (5 ml) and treated dropwise with cyclobutanone (0.11 ml, 1.5 mmol). The mixture was stirred for 30 minutes and then (polystyrylmethyl)trimethylammonium cyanoborohydride (2.0 mmol/g, 1 g, 2 mmol) was added. The reaction mixture was stirred at room temperature for 18 hours, applied to a SCX ion exchange cartridge (Varian bond-elute, 10 g) and washed with methanol and then a mixture of 0.880 ammonia:methanol (1:9). The combined basic fractions were concentrated in vacuo and the resulting residue purified by column chromatography eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:2.25:97.5) to afford the title compound (E225). MS (ES+) m/e 478 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 18 hours
  2. washwashed with methanol
  3. additiona mixture of 0.880 ammonia:methanol (1:9)
  4. concentrationThe combined basic fractions were concentrated in vacuo
  5. customthe resulting residue purified by column chromatography
  6. washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:2.25:97.5)

Sources & evidence

ORD record
ord-7758fe739d57417c99847f81e6e3039e
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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