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

HRID 216920Notes

Reaction equation

HRID 216920 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.[N:30]1([S:34]([C:37]2[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=2)(=[O:36])=[O:35])[CH2:33][CH2:32][CH2:31]1.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:41]=[CH:42][C:37]([S:34]([N:30]3[CH2:31][CH2:32][CH2:33]3)(=[O:36])=[O:35])=[CH:38][CH:39]=2)=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 44886919B-(4-(1-Azetidinylsulfonyl)phenyl)boronic acidHCID 59568595(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 70213622(S)-tert-Butyl 4-(1-amino-3-(4'-(azetidin-1-ylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateYield 77.9%

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), 350 mg) in acetonitrile (7 mL) under nitrogen was treated with 4-(azetidin-1-ylsulfonyl)phenylboronic acid (163 mg) followed by sodium carbonate (0.677 mL). Nitrogen was bubbled through the mixture and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (10 mg) was added. The mixture was stirred at 85° C. for 25 h. The solvent was partially evaporated and the solution was purified by chromatography on silica using ethyl acetate 50-100% in isohexane as eluent to afford the sub-titled compound as a solid (309 mg).

Workup

  1. customNitrogen was bubbled through the mixture and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (10 mg)
  2. additionwas added
  3. customThe solvent was partially evaporated
  4. customthe solution was purified by chromatography on silica

Sources & evidence

ORD record
ord-60376989df2845de8f6256f17621c86b
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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