Ammonium Chloride → N-(1-(4-amino-1-methyl-1H-pyrazol-5-yl)-4-methylazepan-4-yl)acetamide

HRID 1915924Notes

Reaction equation

HRID 1915924 reaction equation
[CH3:1][C:2]1([NH:18][C:19](=[O:21])[CH3:20])[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-])=O)[CH2:4][CH2:3]1.[Cl-].[NH4+]>CCO.O.[Fe]>[NH2:15][C:10]1[CH:11]=[N:12][N:13]([CH3:14])[C:9]=1[N:5]1[CH2:6][CH2:7][CH2:8][C:2]([NH:18][C:19](=[O:21])[CH3:20])([CH3:1])[CH2:3][CH2:4]1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 86680019HCID 86680019, compound

Product 1

HCID 86680124N-(1-(4-amino-1-methyl-1H-pyrazol-5-yl)-4-methylazepan-4-yl)acetamide

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of N-(4-methyl-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl)acetamide (330 mg, 1.11 mmol) in a mixture of EtOH (25 mL) and water (2.5 mL) was added ammonium chloride (300 mg, 5.55 mmol) and iron powder (250 mg, 4.44 mmol). The reaction mixture was heated at 100° C. for 2 hr before being cooled, filtered through Celite® and concentrated under reduced pressure. The residue was partitioned between water (20 mL) and DCM (40 mL) and the organic layer was separated, washed with brine (20 mL), passed through a phase separation cartridge and concentrated under reduced pressure to give N-(1-(4-amino-1-methyl-1H-pyrazol-5-yl)-4-methylazepan-4-yl)acetamide as a brown solid which was used without further purification. Following the procedure for Example 149 using this intermediate and 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)-thiazole-4-carboxylic acid gave 378 as an off-white foam (54 mg, 19% over three steps). 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.86 (s, 1H), 7.39-7.29 (m, 1H), 7.07-6.99 (m, 2H), 6.15 (s, 2H), 5.38 (s, 1H), 3.74 (s, 3H), 3.30-3.18 (m, 4H), 3.12 (ddd, J=13.6, 6.6, 3.1 Hz, 1H), 2.30-2.19 (m, 2H), 2.00-1.72 (m, 6H), 1.45 (s, 3H). LCMS (ES+) m/z 504 (M+1)

Workup

  1. temperaturebefore being cooled
  2. filtrationfiltered through Celite®
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was partitioned between water (20 mL) and DCM (40 mL)
  5. customthe organic layer was separated
  6. washwashed with brine (20 mL)
  7. custompassed through a phase separation cartridge
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b620192cd6fc49af9a071ae4c8831b0a
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

Loading…