Dimethyl Sulfoxide → HCID 90465995, compound

HRID 928548Notes

Reaction equation

HRID 928548 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[NH2:11][N:12]1[C:17]2[C:18]([CH2:29]O)=[CH:19][CH:20]=[C:21]([C:22]3[C:23]([CH3:28])=[N:24][O:25][C:26]=3[CH3:27])[C:16]=2[O:15][CH2:14][CH:13]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:28][C:23]1[C:22]([C:21]2[C:16]3[O:15][CH2:14][CH:13]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[N:12]4[C:17]=3[C:18]([CH:29]=[N:11]4)=[CH:19][CH:20]=2)=[C:26]([CH3:27])[O:25][N:24]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 117777468HCID 117777468, compound

Product 1

HCID 90465995HCID 90465995, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 2.0 M oxalyl chloride in methylene chloride (0.132 mL) at −78° C. was treated with methylene chloride (0.363 mL) followed by dimethyl sulfoxide (0.025 mL, 0.353 mmol) dropwise. The reaction mixture was stirred at −78° C. for 20 min and treated with a solution of [4-amino-8-(3,5-dimethylisoxazol-4-yl)-3-phenyl-3,4-dihydro-2H-1,4-benzoxazin-5-yl]methanol (0.062 g, 0.18 mmol) in methylene chloride (1.50 mL) dropwise. The reaction mixture was stirred at −78° C. for 1 h and treated with triethylamine (0.0984 mL, 0.706 mmol) dropwise. The reaction mixture was stirred at −78° C. for 1 h and warmed to 25° C. The reaction mixture was quenched with water (2 mL) and diluted with methylene chloride (30 mL) and saturated ammonium chloride solution (10 mL). The organic layer was separated, washed with brine, dried over sodium sulfate, filtered, and concentrated to give a tan foam. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min) gave the desired product (19 mg, 32%). 1H NMR (300 MHz, DMSO-d6) δ 8.13 (s, 1H), 7.43 (d, J=8.3 Hz, 1H), 7.39-7.30 (m, 3H), 7.13-7.06 (m, 2H), 7.03 (d, J=8.3 Hz, 1H), 5.90 (dd, J=3.9 Hz, 1H), 4.79 (dd, J=11.6, 3.4 Hz, 1H), 4.69 (dd, J=11.6, 4.6 Hz, 1H), 2.32 (s, 3H), 2.16 (s, 3H). LCMS calculated for C20H18N3O2 (M+H)+: m/z=332.1. found: 332.1.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 1 h
  2. stirringThe reaction mixture was stirred at −78° C. for 1 h
  3. temperaturewarmed to 25° C
  4. customThe reaction mixture was quenched with water (2 mL)
  5. additiondiluted with methylene chloride (30 mL) and saturated ammonium chloride solution (10 mL)
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a tan foam
  12. customPurification via preparative LCMS (XBridge C18 column
  13. washeluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-76271f6773f1424ab814c9acf44b4a21
Source dataset
uspto-grants-2016_03
Patent number
US09290514B2

Reaction notes

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