Diisopropylethylamine → 1,1-dimethylethyl 3-[({3-[(1-methylethyl)oxy]-5-[(4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]phenyl}carbonyl)amino]-1H-pyrazole-1-carboxylate

HRID 548762Notes

Reaction equation

HRID 548762 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][CH:11]([O:13][C:14]1[CH:15]=[C:16]([CH:20]=[C:21]([O:23][C:24]2[CH:36]=[CH:35][C:27]3[C:28](=[O:34])[N:29]([CH3:33])[CH2:30][CH2:31][O:32][C:26]=3[CH:25]=2)[CH:22]=1)[C:17](O)=[O:18])[CH3:12].[NH2:37][C:38]1[CH:42]=[CH:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[N:39]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:12][CH:11]([O:13][C:14]1[CH:15]=[C:16]([C:17]([NH:37][C:38]2[CH:42]=[CH:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[N:39]=2)=[O:18])[CH:20]=[C:21]([O:23][C:24]2[CH:36]=[CH:35][C:27]3[C:28](=[O:34])[N:29]([CH3:33])[CH2:30][CH2:31][O:32][C:26]=3[CH:25]=2)[CH:22]=1)[CH3:10]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 51358380tert-Butyl 3-amino-1H-pyrazole-1-carboxylateHCID 576632203-[(1-Methylethyl)oxy]-5-[(4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]benzoic acid

Product 1

HCID 576631971,1-dimethylethyl 3-[({3-[(1-methylethyl)oxy]-5-[(4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]phenyl}carbonyl)amino]-1H-pyrazole-1-carboxylateYield 11.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.26 mL, 1.5 mmol) was added to a solution of 3-[(1-methylethyl)oxy]-5-[(4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]benzoic acid (185 mg, 0.5 mmol), 1,1-dimethylethyl 3-amino-1H-pyrazole-1-carboxylate (110 mg, 0.6 mmol) and HATU (247 mg, 0.65 mmol) in DMF (2 mL) and the mixture stirred at RT for 16 hours. The mixture was poured onto water (30 mL), extracted with ethyl acetate (3×15 mL), the combined organic extracts washed with 1N citric acid, saturated sodium hydrogen carbonate, brine, dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica, eluting with 60% ethyl acetate in isohexane, to give the desired compound (32 mg). 1H NMR δ (CDCl3): 1.3 (d, 6H), 1.55 (s, 9H), 3.15 (s, 3H), 3.5 (t, 2H), 4.3 (t, 2H), 4.5 (m, 1H), 6.5 (s, 1H), 6.7 (m, 2H), 7.1 (d, 1H), 7.8 (d, 1H), 7.95 (d, 1H), 8.7 (s, 1H); m/z 535 (M−H)−

Workup

  1. additionThe mixture was poured onto water (30 mL)
  2. extractionextracted with ethyl acetate (3×15 mL)
  3. washthe combined organic extracts washed with 1N citric acid, saturated sodium hydrogen carbonate, brine
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was chromatographed on silica
  7. washeluting with 60% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-6f32c3ed2e354484b0d192ef573d0711
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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