Hydrazine hydrate (1:1) → 3-Cyclobutyl-7-([5-(1H-pyrazol-5-yl)-2-pyridinyl]oxy}-2,3,4,5-tetrahydro-1H-3-benzazepine

HRID 641516Notes

Reaction equation

HRID 641516 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([O:16][C:17]4[N:22]=[CH:21][C:20]([C:23](=O)/[CH:24]=[CH:25]/[N:26](C)C)=[CH:19][CH:18]=4)=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.O.[NH2:31]N>CO>[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([O:16][C:17]4[CH:18]=[CH:19][C:20]([C:23]5[NH:31][N:26]=[CH:25][CH:24]=5)=[CH:21][N:22]=4)=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 57463646(2E)-1-{6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-3-(dimethylamino)-2-propen-1-one

Product 1

HCID 100214413-Cyclobutyl-7-([5-(1H-pyrazol-5-yl)-2-pyridinyl]oxy}-2,3,4,5-tetrahydro-1H-3-benzazepine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of (2E)-1-{6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-3-(dimethylamino)-2-propen-1-one (D53) (195 mg, 0.5 mmol) and hydrazine hydrate (0.4 ml) in methanol (3 ml) was heated at reflux for 24 hours. The reaction mixture was cooled and 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 (1:9:90) to afford the title compound (E215). MS (ES+) m/e 361 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 24 hours
  3. temperatureThe reaction mixture was cooled
  4. washwashed with methanol
  5. additiona mixture of 0.880 ammonia/methanol (1:9)
  6. concentrationThe combined basic fractions were concentrated in vacuo
  7. customthe resulting residue purified by column chromatography
  8. washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (1:9:90)

Sources & evidence

ORD record
ord-d0a1314bb52f42899322818c59d0a9ca
Source dataset
uspto-grants-2010_04
Patent number
US07696193B2

Reaction notes

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