Sodium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216929Notes

Reaction equation

HRID 216929 reaction equation
[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1.[CH3:30][N:31]1[C:36](=[O:37])[CH2:35][O:34][C:33]2[CH:38]=[CH:39][C:40](B3OC(C)(C)C(C)(C)O3)=[CH:41][C:32]1=2.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:40]2[CH:39]=[CH:38][C:33]3[O:34][CH2:35][C:36](=[O:37])[N:31]([CH3:30])[C:32]=3[CH:41]=2)=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 532172054-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-2H-benzo[B][1,4]oxazin-3(4H)-oneHCID 59568595(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 59568612(S)-tert-Butyl 4-(1-amino-3-(4-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateYield 52.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 1, step (iii), 276 mg) in acetonitrile (7 mL) under nitrogen was treated with 4-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (Example 10, step (ii), 154 mg) followed by sodium carbonate (0.533 mL). Nitrogen was bubbled through the mixture and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added. The mixture was stirred at 85° C. for 25 h and then allowed to cool. The solution was absorbed onto silica and purified by chromatography on silica using ethyl acetate 50-100% in isohexane as eluent to afford the sub-titled compound (155 mg).

Workup

  1. customNitrogen was bubbled through the mixture and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 mg)
  2. additionwas added
  3. temperatureto cool
  4. customThe solution was absorbed onto silica
  5. custompurified by chromatography on silica

Sources & evidence

ORD record
ord-8b0dc419fd2a4f4c835b8f882b275879
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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