2-Fluoroaniline → HCID 10309468, compound

HRID 1169268Notes

Reaction equation

HRID 1169268 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:13](=[O:14])[C:12]2[S:15][CH:16]=[CH:17][C:11]=2[N:10]=[C:9]1[CH:18]=O.[F:20][C:21]1[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=1[NH2:23].S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:13](=[O:14])[C:12]2[S:15][CH:16]=[CH:17][C:11]=2[N:10]=[C:9]1[CH2:18][NH:23][C:22]1[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=1[F:20]

Participants

7

Reactant 5

HCID 95842-FluoroanilineHCID 24436Sodium SulfateHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 12088010HCID 12088010, compound

Product 1

HCID 10309468HCID 10309468, compoundYield 39.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 3-(2-chloro-phenyl)-4-oxo-3,4-dihydro-thieno[3,2-d]pyrimidine-2-carboxaldehyde (0.435 g, 1.5 mmol), 2-fluoroaniline (0.121 mL, 1.25 mmol), and anhydrous sodium sulfate (2.1 g 15 mmol) in glacial acetic acid (10 mL) was stirred overnight at ambient temperature. Sodium triacetoxyborohydride (0.795 g, 3.75 mmol) was added in one portion and the reaction was stirred for four hours. The reaction was carefully poured into saturated aqueous sodium bicarbonate and repeatedly extracted with methylene chloride. The combined organic phase was washed with water and brine, dried over sodium sulfate and concentrated. The residue was flash chromatographed on silica gel eluting with 2:1 hexane/ethyl acetate. After elution of a 50 mL forerun, 15 mL fractions were collected. Fractions 3-12 were combined and concentrated to afford 0.190 g (39%) of 3-(2-chloro-phenyl)-2-[(2-fluoro-phenylamino)-methyl]-3H-thieno[3,2-d]pyrimidin-4-one as a tan solid which had: mp 175-176° C.; 1H NMR δ 7.84 (d, J=5.5 Hz, 1H), 7.66 (dd, J=1.5, 8 Hz, 1h), 7.53 (sym m, 2H), 7.42 (d, J=5.5 Hz, 1H), 7.37 (dd, J=2, 7 Hz, 1H), 6.97 (ddd, J=1.5, 8, 11.5 Hz, 1H), 6.90 (t, J=7.5 Hz, 1H), 6.63 (sym m, 1H), 6.40 (dt, J=1.5, 9 Hz, 1H), 5.17 (br s, 1H), 3.96 (dd, J=5.5, 17 Hz, 1H), 3.87 (dd, J=5, 17 Hz, 1H). Analysis calculated for C19H13ClFN3OS: C, 59.15; H, 3.40; N, 10.89. Found: C, 58.96; H, 3.41; N, 11.17.

Workup

  1. stirringthe reaction was stirred for four hours
  2. extractionrepeatedly extracted with methylene chloride
  3. washThe combined organic phase was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customchromatographed on silica gel eluting with 2:1 hexane/ethyl acetate
  7. washAfter elution of a 50 mL forerun
  8. custom15 mL fractions were collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-e39ef781c31e4193bbf9b0e05614c240
Source dataset
uspto-grants-2003_09
Patent number
US06627755B1

Reaction notes

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