Ammonium formate → HCID 86679985, compound

HRID 1915774Notes

Reaction equation

HRID 1915774 reaction equation
[CH3:1][C:2]1([OH:18])[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.C([O-])=O.[NH4+]>CO.[Pd]>[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]([CH3:1])([OH:18])[CH2:3][CH2:4]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 86679984HCID 86679984, compound

Product 1

HCID 86679985HCID 86679985, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-methyl-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ol (212 mg, 0.83 mmol) in MeOH (15 mL) was added ammonium formate (386 mg, 5.63 mmol) and 10% palladium on carbon (88 mg, 0.83 mmol) and the mixture was heated at 80° C. for 18 hr. The mixture was filtered through Celite® and the filtrate concentrated under reduced pressure. The residue was partitioned between DCM (20 mL) and water (20 mL) and the aqueous layer was re-extracted with DCM (3×20 mL). The combined organic layers were passed through a phase separation cartridge and concentrated under reduced pressure to give 1-(4-amino-1-methyl-1H-pyrazol-5-yl)-4-methylazepan-4-ol as a red oil. To a solution of this oil (140 mg, 0.623 mmol) in DCM (25 mL) was added 2-bromo-5-(tert-butoxycarbonylamino)thiazole-4-carboxylic acid (241 mg, 0.75 mmol), PyBOP (454 mg, 1.94 mmol) and DIPEA (0.17 mL, 1.0 mmol) and the mixture was stirred at room temperature for 16 hr. Water (20 ml) was added and the mixture was diluted with DCM (100 mL). The organic layer was washed with water (20 mL), separated, dried over MgSO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave tert-butyl 2-bromo-4-(5-(4-hydroxy-4-methylazepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate as an off-white solid (280 mg, 63% over two steps). 1H NMR (400 MHz, CDCl3) δ 10.49 (s, 1H), 9.41 (s, 1H), 7.95 (s, 1H), 3.71 (s, 3H), 3.41-3.30 (m, 1H), 3.24-3.11 (m, 3H), 2.39 (br s, 1H), 2.07-1.75 (m, 5H), 1.84-1.78 (m, 1H), 1.52 (s, 9H), 1.43 (s, 3H).

Workup

  1. filtrationThe mixture was filtered through Celite®
  2. concentrationthe filtrate concentrated under reduced pressure
  3. customThe residue was partitioned between DCM (20 mL) and water (20 mL)
  4. extractionthe aqueous layer was re-extracted with DCM (3×20 mL)
  5. customThe combined organic layers were passed through a phase separation cartridge
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3034d23e1c4f43eb8714252344872770
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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