Pyridine → 1,1-dimethylethyl 3-[({3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(3-methyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]phenyl}carbonyl)amino]-1H-pyrazole-1-carboxylate

HRID 548732Notes

Reaction equation

HRID 548732 reaction equation
ClC(N(C)C)=C(C)C.[CH3:9][C@H:10]([O:14][C:15]1[CH:16]=[C:17]([CH:21]=[C:22]([O:24][C:25]2[CH:36]=[CH:35][C:28]3[C:29](=[O:34])[N:30]([CH3:33])[CH2:31][O:32][C:27]=3[CH:26]=2)[CH:23]=1)[C:18]([OH:20])=O)[CH2:11][O:12][CH3:13].[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.N1C=CC=CC=1>C(Cl)Cl>[CH3:9][C@H:10]([O:14][C:15]1[CH:16]=[C:17]([C:18]([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:20])[CH:21]=[C:22]([O:24][C:25]2[CH:36]=[CH:35][C:28]3[C:29](=[O:34])[N:30]([CH3:33])[CH2:31][O:32][C:27]=3[CH:26]=2)[CH:23]=1)[CH2:11][O:12][CH3:13]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 51358380tert-Butyl 3-amino-1H-pyrazole-1-carboxylateHCID 576631913-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(3-methyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]benzoic acid

Product 1

HCID 576632111,1-dimethylethyl 3-[({3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(3-methyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]phenyl}carbonyl)amino]-1H-pyrazole-1-carboxylateYield 52.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.13 mL, 0.97 mmol) was added to a solution of 3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(3-methyl-4-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)oxy]benzoic acid (0.25 g, 0.65 mmol) in DCM (10 mL) and stirred for 1 hour. 1,1-Dimethylethyl 3-amino-1H-pyrazole-1-carboxylate (0.18 g, 0.97 mmol) then pyridine (0.11 mL, 1.29 mmol) were added and the reaction stirred for a further 45 mins then reduced in vacuo and partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was further extracted into ethyl acetate (50 mL) and the combined organics washed with water (50 mL), brine (50 mL), dried (MgSO4), and reduced in vacuo. The crude oil was chromatographed on silica, eluting with 40-100% ethyl acetate in isohexane, to give the desired compound as a golden oil (0.19 g). 1H NMR δ (CDCl3): 1.32 (d, 3H), 1.63 (s, 9H), 3.10 (s, 3H), 3.40 (s, 3H), 3.48-3.60 (m, 2H), 4.56-4.60 (m, 1H), 5.18 (s, 2H), 6.54 (d, 1H), 6.73-6.76 (m, 1H), 6.83 (t, 1H), 7.07-7.08 (m, 2H), 7.25-7.26 (m, 1H), 7.95 (d, 1H), 8.00 (d, 1H), 8.65 (s, 1H); m/z 551 (M−H)−

Workup

  1. stirringthe reaction stirred for a further 45 mins
  2. custompartitioned between ethyl acetate (50 mL) and water (50 mL)
  3. extractionThe aqueous layer was further extracted into ethyl acetate (50 mL)
  4. washthe combined organics washed with water (50 mL), brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. customThe crude oil was chromatographed on silica
  7. washeluting with 40-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-527929032d744d3e81f1d228b9b5d771
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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