Ammonium formate → 3-[(4-Methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

HRID 548714Notes

Reaction equation

HRID 548714 reaction equation
Cl[C:2]1[C:12]2[O:11][CH2:10][CH2:9][N:8]([CH3:13])[C:7](=[O:14])[C:6]=2[CH:5]=[CH:4][C:3]=1[O:15][C:16]1[CH:17]=[C:18]([CH:28]=[C:29]([O:31][C@H:32]2[CH2:36][CH2:35][O:34][CH2:33]2)[CH:30]=1)[C:19]([NH:21][C:22]1[CH:26]=[CH:25][N:24]([CH3:27])[N:23]=1)=[O:20].C([O-])=O.[NH4+]>C(O)C.[Pd]>[CH3:13][N:8]1[C:7](=[O:14])[C:6]2[CH:5]=[CH:4][C:3]([O:15][C:16]3[CH:17]=[C:18]([CH:28]=[C:29]([O:31][C@H:32]4[CH2:36][CH2:35][O:34][CH2:33]4)[CH:30]=3)[C:19]([NH:21][C:22]3[CH:26]=[CH:25][N:24]([CH3:27])[N:23]=3)=[O:20])=[CH:2][C:12]=2[O:11][CH2:10][CH2:9]1

Participants

5

Reactant 2

HCID 2723923Ammonium formate2×HCID 159495913-[(9-Chloro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

Product 1

HCID 159495923-[(4-Methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamideYield 68.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

3-[(9-Chloro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide (150 mg, 0.29 mmol) was dissolved in ethanol (5 mL) and ammonium formate (147 mg, 2.33 mmol) was added in one portion. The reaction was blanketed with argon and 10% palladium on charcoal (10 mg) was added. The mixture was heated to 140° C. for a total of 55 minutes in a Smith Creator microwave reactor after which time a further 100 mgs of ammonium formate and 10 mgs of catalyst were added and the suspension heated for a further hour. The catalyst was filtered off and the volatiles removed in vacuo to give the crude product as a colourless oil. This residue was purified by reverse phase preparative HPLC, eluting with 5-95% acetoniltrile in water (+0.2% TFA), to give the title compound as a colourless foam (95 mg). 1H NMR δ (CDCl3): 2.12-2.19 (1H, m), 2.23-2.32 (1H, m), 3.23 (3H, s), 3.59 (2H, t), 3.88-3.91 (4H, m), 4.01 (3H, m), 4.42 (2H, t), 5.15-5.17 (1H, m), 6.61 (5H, d), 6.78-6.79 (1H, m), 6.80 (1H, t), 7.02 (1H, d), 7.33-7.36 (2H, m), 7.38-7.40 (1H, m), 7.85 (1H, d), 10.58 (1H, s); m/z 479 (M+H)+.

Workup

  1. additionwas added
  2. additionwere added
  3. temperaturethe suspension heated for a further hour
  4. filtrationThe catalyst was filtered off
  5. customthe volatiles removed in vacuo
  6. customto give the crude product as a colourless oil
  7. customThis residue was purified by reverse phase preparative HPLC
  8. washeluting with 5-95%

Sources & evidence

ORD record
ord-bc0c7922d3b44bedb0216246adef797b
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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