Formamide → HCID 66780007, compound

HRID 1958047Notes

Reaction equation

HRID 1958047 reaction equation
[Cl:1][C:2]1[C:3]([CH3:27])=[C:4]([CH2:8][N:9]2[C:14]3[N:15]=[C:16]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[S:17][C:13]=3[C:12](=[O:24])[N:11]=[C:10]2SC)[CH:5]=[CH:6][CH:7]=1.C([NH2:30])=O>O>[NH2:30][C:10]1[N:9]([CH2:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[CH3:27])[C:14]2[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[S:17][C:13]=2[C:12](=[O:24])[N:11]=1

Participants

4

Reactant 2

HCID 713FormamideHCID 66780292HCID 66780292, compound

Product 1

HCID 66780007HCID 66780007, compoundYield 32.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
198 °C

Procedure

4-[(3-chloro-2-methylphenyl)methyl]-5-(methylthio)-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (500 mg, 1.182 mmol) in formamide (8 ml, 201 mmol) was heated at 192° C. and stirred for 1 h. The temperature was increased to 198° C. and stirring was continued for additional 3 h. After cooling, water was added in and the precipitate was collected, washed with water, then Et2O and dried to give 437 mg of crude. The material was purified by prep HPLC on a Kromasil Silica 5u 60 A 21×250 mm column, eluting with 95:5—CHCl3:CH3OH (2M NH3) at 20 mL/min and collecting fraction at about 7.2 min. 5-amino-4-[(3-chloro-2-methylphenyl)methyl]-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (151 mg, 0.380 mmol, 32.1% yield) was obtained from the crude as an off white powder. LC/MS (ES) m/z=392.1 (M+H); 1H NMR (400 MHz, DMSO-d6) δ ppm 7.36 (d, J=7.83 Hz, 1H), 7.16 (t, J=7.96 Hz, 1H), 6.97 (s, 2H), 6.51 (d, J=7.58 Hz, 1H), 5.31 (s, 2H), 3.61-3.70 (m, 4H), 3.42 (t, J—=4.80 Hz, 4H), 2.38 (s, 3H)

Workup

  1. stirringstirring
  2. waitwas continued for additional 3 h
  3. temperatureAfter cooling
  4. customwas collected
  5. washwashed with water
  6. dry with materialEt2O and dried
  7. customto give 437 mg of crude
  8. customThe material was purified by prep HPLC on a Kromasil Silica 5u 60 A 21×250 mm column
  9. washeluting with 95
  10. custom5—CHCl3:CH3OH (2M NH3) at 20 mL/min and collecting fraction at about 7.2 min

Sources & evidence

ORD record
ord-78454653e1834e29b6574905a263165e
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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