(R)-5-bromo-2-oxo-3-(1-phenylethyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide → HCID 117629625, compound

HRID 920274Notes

Reaction equation

HRID 920274 reaction equation
Br[C:2]1[C:3]([S:20]([NH:23][C:24]2[S:28][N:27]=[CH:26][N:25]=2)(=[O:22])=[O:21])=[CH:4][C:5]2[O:9][C:8](=[O:10])[N:7]([C@@H:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH3:12])[C:6]=2[CH:19]=1.[CH2:29]([Zn]CC)[CH3:30]>CN1C(=O)CCC1.O.CCOC(C)=O.CC(C1C=C(C(C)C)C(C2C=CC=C(P(C3CCCCC3)C3CCCCC3)C=2)=C(C(C)C)C=1)C.C1C=[C-]C(C2C(N)=CC=CC=2)=CC=1.Cl[Pd+]>[CH2:29]([C:2]1[C:3]([S:20]([NH:23][C:24]2[S:28][N:27]=[CH:26][N:25]=2)(=[O:22])=[O:21])=[CH:4][C:5]2[O:9][C:8](=[O:10])[N:7]([C@@H:11]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH3:12])[C:6]=2[CH:19]=1)[CH3:30]

Participants

7

Reactant 2

HCID 89533806(R)-5-bromo-2-oxo-3-(1-phenylethyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamideHCID 178418750HCID 178418750, compound

Product 1

HCID 117629625HCID 117629625, compound

Reagents, catalysts & solvents 4

HCID 72376365[2-(2-Aminophenyl)phenyl]-chloro-palladium dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphaneCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

Into a solution of (R)-5-bromo-2-oxo-3-(1-phenylethyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (38-1, 80 mg, 0.166 mmol, prepared from 35-3 by a reaction sequence analogous to that described herein) in NMP (831 ul) was added diethylzinc (1M in hexanes, 0.499 mmol) followed by chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (7 mg, 8.9 umol). The reaction vessel was sealed and heated to 120° C. for 12 h, cooled to rt, diluted with 1 ml of H2O and 3 ml of EtOAc, filtered through celite, concentrated and purified by reversed phase HPLC (2 cm×5 cm C18, acetonitrile-water gradient, 0.05% TFA added) to yield 5-ethyl-2-oxo-3-[(1R)-1-phenylethyl]-N-1,2,4-thiadiazol-5-yl-2,3-dihydro-1,3-benzoxazole-6-sulfonamide (38-2). 1H NMR (499 MHz, DMSO): δ 8.44 (s, 1H); 7.75 (s, 1H); 7.46 (d, J=7.7 Hz, 2H); 7.36-7.38 (m, 3H); 7.06 (s, 1H); 5.63 (d, J=7.3 Hz, 1H); 2.92-2.94 (m, 2H); 1.88 (d, J=7.1 Hz, 3H); 1.09 (t, J=7.4 Hz, 3H). LRMS C19H18N404S2 [M+H] calc 431.1, obs 431.0.

Workup

  1. customThe reaction vessel was sealed
  2. temperaturecooled to rt
  3. filtrationfiltered through celite,
  4. concentrationconcentrated
  5. custompurified by reversed phase HPLC (2 cm×5 cm C18, acetonitrile-water gradient, 0.05% TFA added)

Sources & evidence

ORD record
ord-a56939f46f31417b8e0b336a194df1ab
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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