Sodium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216967

Reaction equation

HRID 216967 reaction equation
[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=1.Br[C:39]1[CH:40]=[CH:41][C:42]2[NH:47][C:46](=[O:48])[CH2:45][S:44][C:43]=2[CH:49]=1.[C:50](=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1)=[O:22])[CH2:4][C:5]1[CH:6]=[CH:7][C:8]([C:39]2[CH:40]=[CH:41][C:42]3[N:47]([CH3:50])[C:46](=[O:48])[CH2:45][S:44][C:43]=3[CH:49]=2)=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 6890657-Bromo-2H-(1,4)-benzothiazin-3(4h)-oneHCID 59568592(S)-tert-Butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 59568625(S)-tert-Butyl 4-(1-amino-3-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-7-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

(S)-tert-Butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 241 mg) in acetonitrile (8 mL) with 7-bromo-4-methyl-2H-benzo[b][1,4]thiazin-3(4H)-one (Example 28, step (i), 120 mg) was treated with aqueous sodium carbonate solution (2M, 0.465 mL) and then nitrogen was bubbled through the mixture. 1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added and the mixture was heated at 85° C. under nitrogen for 18 h. A further addition of sodium carbonate solution (2M, 0.2 mL) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was made and the mixture was heated at 85° C. for a further 18 h. A further addition of (S)-tert-butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 20 mg) was made and the mixture was heated at 85° C. for 18 h. The mixture was purified by chromatography on silica eluting with ethyl acetate/isohexane (50:50 to 100:0) to afford the sub-titled compound (132 mg).

Workup

  1. customnitrogen was bubbled through the mixture
  2. addition1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added
  3. additionA further addition of sodium carbonate solution (2M, 0.2 mL) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 mg)
  4. temperaturethe mixture was heated at 85° C. for a further 18 h
  5. additionA further addition of (S)-tert-butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 20 mg)
  6. temperaturethe mixture was heated at 85° C. for 18 h
  7. customThe mixture was purified by chromatography on silica eluting with ethyl acetate/isohexane (50:50 to 100:0)

Sources & evidence

ORD record
ord-e16f060404284ef8bfbac929dae84aee
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Linked notes

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