Chloroform → HCID 57818738, compound

HRID 705595Notes

Reaction equation

HRID 705595 reaction equation
[F:1][C:2]1[C:3]([NH2:17])=[N:4][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[N:6][CH:7]=1.[C:18](=[O:21])(O)[O-].[Na+].[C:23](Cl)(Cl)=[S:24].[CH:27](Cl)(Cl)Cl>O>[F:1][C:2]1[C:3]([NH:17][C:23](=[S:24])[O:21][CH2:18][CH3:27])=[N:4][C:5]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 6212Chloroform2×HCID 10040ThiophosgeneHCID 516892Sodium BicarbonateHCID 578185745-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine

Product 1

HCID 57818738HCID 57818738, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine (300 mg, 1.26 mmol) was stirred in chloroform (25 mL) and water (12 mL). Sodium bicarbonate (870 mg, 10.12 mmol) was added followed by dropwise addition of thiophosgene (218 mg, 1.9 mmol). The reaction mixture was stirred at room temperature for 16 hours, then diluted with chloroform (20 mL) and the phases were separated. The organic extract was dried over sodium sulfate, filtered, and concentrated by rotary evaporation to ⅓ volume. To this chloroform solution of crude isothiocyanate was added abs. ethanol (10 mL) and the mixture was heated in a sealed tube for 1 h. The reaction mixture was cooled to room temperature, concentrated and purified by flash chromatography on silica, to give 45 mg (11%) of O-ethyl 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylcarbamothioate as a pale yellow solid: mp 109-119° C.; 1H NMR (CDCl3) δ 8.30 (bs, 2H), 7.44 (m, 2H), 7.06 (m, 2H), 5.36 (s, 2H), 4.66 (q, J=6 Hz, 2H), 1.45 (t, J=6 Hz, 3H); HPLC-MS (ESI): m/z 326 (ES+).

Workup

  1. customthe phases were separated
  2. extractionThe organic extract
  3. dry with materialwas dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. additionTo this chloroform solution of crude isothiocyanate was added abs
  7. temperatureethanol (10 mL) and the mixture was heated in a sealed tube for 1 h
  8. temperatureThe reaction mixture was cooled to room temperature
  9. concentrationconcentrated
  10. custompurified by flash chromatography on silica

Sources & evidence

ORD record
ord-647f448736164790a3af20956dcbd8b0
Source dataset
uspto-grants-2015_11
Patent number
US09174970B2

Reaction notes

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