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

HRID 548744Notes

Reaction equation

HRID 548744 reaction equation
ClC(N(C)C)=C(C)C.[CH3:9][N:10]1[CH2:16][CH2:15][O:14][C:13]2[CH:17]=[C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][CH3:35])[CH:30]=3)[C:25](O)=[O:26])[CH:19]=[CH:20][C:12]=2[S:11]1(=[O:38])=[O:37].[NH2:39][C:40]1[CH:44]=[CH:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[N:41]=1.N1C=CC=CC=1>C(Cl)Cl.O.C(OCC)(=O)C>[CH3:9][N:10]1[CH2:16][CH2:15][O:14][C:13]2[CH:17]=[C:18]([O:21][C:22]3[CH:23]=[C:24]([C:25]([NH:39][C:40]4[CH:44]=[CH:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[N:41]=4)=[O:26])[CH:28]=[C:29]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][CH3:35])[CH:30]=3)[CH:19]=[CH:20][C:12]=2[S:11]1(=[O:37])=[O:38]

Participants

8

Reactant 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 51358380tert-Butyl 3-amino-1H-pyrazole-1-carboxylateHCID 57663179HCID 57663179, compound

Product 1

HCID 576631951,1-dimethylethyl 3-{[(3-[(2-methyl-1,1-dioxido-3,4-dihydro-2H-5,1,2-benzoxathiazepin-7-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}phenyl)carbonyl]amino}-1H-pyrazole-1-carboxylateYield 16.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.13 mL, 1.01 mmol) was added to a solution of 3-[(2-methyl-1,1-dioxido-3,4-dihydro-2H-5,1,2-benzoxathiazepin-7-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}benzoic acid (0.22 g, 0.50 mmol) in DCM (8 mL) and stirred for 1 hour. 1,1-Dimethylethyl 3-amino-1H-pyrazole-1-carboxylate (231 mg, 1.26 mmol) then pyridine (0.1 mL, 1.26 mmol) were added and the reaction stirred until the reaction was complete. The reaction mixture was reduced in vacuo and ethyl acetate (50 mL) and water (50 mL) were added. 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), filtered and reduced in vacuo to give a golden oil which was chromatographed on silica, eluting with 25-70% ethyl acetate in isohexane then 0-5% methanol in DCM, to give the desired compound as a colourless oil (50 mg).

Workup

  1. stirringthe reaction stirred until the reaction
  2. additionwere added
  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. filtrationfiltered
  7. customto give a golden oil which
  8. customwas chromatographed on silica
  9. washeluting with 25-70% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-edf7184f8a4d45439d1c3c719f533d3f
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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