Sodium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4'-(morpholinosulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216965

Reaction equation

HRID 216965 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:44]=[CH:43][C:42]([S:45]([N:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)(=[O:47])=[O:46])=[CH:41][CH:40]=1.C(=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]([CH3:33])([CH3:35])[CH3:34])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:39]2[CH:44]=[CH:43][C:42]([S:45]([N:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)(=[O:47])=[O:46])=[CH:41][CH:40]=2)=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2531284-[(4-Bromobenzene)sulfonyl]morpholineHCID 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 59568573(S)-tert-Butyl 4-(1-amino-3-(4'-(morpholinosulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateYield 80.5%

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), 250 mg) in acetonitrile (8 mL) with 4-(4-bromophenylsulfonyl)morpholine (148 mg) was treated with aqueous sodium carbonate (2M, 0.5 mL) and 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. for 18 h under nitrogen. The reaction mixture was evaporated onto silica and purified by chromatography on silica eluting with ethyl acetate/isohexane (50:50 to 100:0) to afford the sub-titled compound (240 mg).

Workup

  1. customwas bubbled through the mixture
  2. addition1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added
  3. customThe reaction mixture was evaporated onto silica
  4. custompurified by chromatography on silica eluting with ethyl acetate/isohexane (50:50 to 100:0)

Sources & evidence

ORD record
ord-1a89f85327c742928b7a8c64219f76c9
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Linked notes

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