1,1'-Carbonyldiimidazole → HCID 11153898, compound

HRID 899220Notes

Reaction equation

HRID 899220 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[C:11]([Cl:16])[CH:10]=2)=[CH:4][C:3]=1[C:17](=[O:20])[CH2:18][CH3:19].[S:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[Li].C1N=CN([C:32](N2C=NC=C2)=[O:33])C=1>C1COCC1>[Cl:16][C:11]1[CH:10]=[C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]3[NH:1][C:32](=[O:33])[O:20][C:17]([CH2:18][CH3:19])([C:22]4[S:21][CH:25]=[CH:24][CH:23]=4)[C:3]=3[CH:4]=2)[CH:14]=[CH:13][C:12]=1[F:15]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 69215960HCID 69215960, compoundHCID 178418439HCID 178418439, compound

Product 1

HCID 11153898HCID 11153898, compoundYield 5.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-{2-amino-5-[(3-chloro-4-fluorophenyl)amino]-phenyl}propan-1-one (2.40 g, 8.20 mmol) in THF (80 mL) was added 1.0M thienyllithium (32 mL, 32 mmol) slowly at 0° C. over 20 minutes. The reaction was stirred overnight at room temperature, quenched with ammonium chloride solution (sat.), and extracted with ethyl acetate several times. The organic layer washed with brine and dried over magnesium sulfate. The concentrated crude material was dissolved in THF (40 mL). CDI (2.66 g, 16.40 mmol) was added and the reaction was stirred overnight at room temperature. The reaction solution was partitioned between ammonium chloride solution (sat.) and ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. Flash silica gel column separation with 30% ethyl acetate/hexane followed by trituration with methylene chloride/ether gave 6-[(3-chloro-4-fluorophenyl)amino]-4-ethyl-4-thien-2-yl-1,4-dihydro-2H-3,1-benzoxazin-2-one as a white solid (0.19 g, 5%). 1H NMR (DMSO-d6): δ 10.22 (s, 1H), 8.20 (s, 1H), 7.53 (dd, J=5.0, 1.3 Hz, 1H), 7.24 (t, J=9.0 Hz, 1H), 7.07 (dd, J=8.5, 2.3 Hz, 1H), 7.0 (m, 3H), 6.92 (dd, J=3.6, 1.3 Hz, 1H), 6.88 (m, 2H), 2.43 (m, 2H), 0.96 (t, J=7.1 Hz, 3H); MS (ESI) m/z 403/405 ([M+H]+); MS (ESI) m/z 401/403 ([M−H]−); HRMS: calcd for C20H16ClFN2O2S, 402.0605; found (ESI+), 403.06762; Anal. calcd for C20H16ClFN2O2S: C, 59.63; H, 4.00; N, 6.95. Found: C, 59.79; H, 4.35; N, 6.55.

Workup

  1. customquenched with ammonium chloride solution (sat.)
  2. extractionextracted with ethyl acetate several times
  3. washThe organic layer washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationThe concentrated crude material
  6. dissolutionwas dissolved in THF (40 mL)
  7. stirringthe reaction was stirred overnight at room temperature
  8. customThe reaction solution was partitioned between ammonium chloride solution (sat.) and ethyl acetate
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. concentrationconcentrated
  11. customFlash silica gel column separation with 30% ethyl acetate/hexane

Sources & evidence

ORD record
ord-fa77b81861b8400289db291f5df762e1
Source dataset
uspto-grants-2008_04
Patent number
US07354915B2

Reaction notes

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