1-Propanol → HCID 44816636, compound

HRID 1697972Notes

Reaction equation

HRID 1697972 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[CH2:27][CH2:26][N:25]([C:28]4[N:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[CH2:24][C:9]=3[N:10]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20](SC)=[NH:21])=[CH:15][CH:14]=3)[N:12]=2)[CH2:3][CH2:2]1.C(O)CC.[CH2:38]([NH2:40])[CH3:39]>>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[CH2:27][CH2:26][N:25]([C:28]4[N:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[CH2:24][C:9]=3[N:10]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20]4[NH:40][CH:38]=[CH:39][N:21]=4)=[CH:15][CH:14]=3)[N:12]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 10311-PropanolHCID 6341Ethylamine3×HCID 178503971HCID 178503971, compound

Product 1

HCID 44816636HCID 44816636, compound

Conditions

Temperature
97 °C

Procedure

Methyl 4-(4-morpholino-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenylcarbamimidothioate (0.070 g, 0.00015 mol) in 1-Propanol (5.00 mL, 0.0669 mol) was added Ethanamine, 2,2-diethoxy- (0.0664 mL, 0.000454 mol) heated at 97° C. for 2 hours. At this time, an additional portion of Ethanamine, 2,2-diethoxy- (0.0222 mL, 0.000152 mol) was added to the reaction mixture and stirred for 1 hour at 97° C. After this time, an additional portion of Ethanamine, 2,2-diethoxy- (0.0222 mL, 0.000152 mol) was added to the reaction mixture and heated at 97° C. for 6 hours. The reaction mixture was concentrated and dried in vacuo overnight. The crude product was cooled at 0° C. and then added 10.0 M of Hydrogen chloride in Water (2.00 mL), allowed to warm slowly to room temperature, stirred for 6 hours, then poured into ice, and to the ice solution was added saturated NaHCO3 until the pH was approximately 9. The aqueous solution was extracted three times with 10% MeOH in dichloromethane, dried over Magnesium sulfate, filtered, and concentrated to provide the crude product which was chromatographed through silica gel (4 g, 0-10% MeOH in dichloromethane), and further purified by HPLC. 1-(4-(4-morpholino-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-1H-imidazol-2-amine (tz) 1H NMR (400 MHz, DMSO) δ 8.44 (t, J=6.7, 3H), 8.23 (s, 1H), 7.58 (d, J=8.7, 2H), 6.93 (d, J=1.5, 1H), 6.71 (t, J=4.7, 1H), 6.59 (d, J=1.5, 1H), 5.52 (s, 2H), 4.86 (s, 2H), 4.00 (t, J=5.1, 2H), 3.74 (d, J=4.5, 4H), 3.52 (d, J=4.4, 4H), 2.79 (s, 2H). LC/MS-m/z+456.2 (M+H)+; and N-(4-(4-morpholino-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-1H-imidazol-2-amine (ty) LC/MS-m/z+456.2 (M+H)+.

Workup

  1. temperatureheated at 97° C. for 6 hours
  2. concentrationThe reaction mixture was concentrated
  3. customdried in vacuo overnight
  4. temperatureThe crude product was cooled at 0° C.
  5. additionadded 10.0 M of Hydrogen chloride in Water (2.00 mL)
  6. temperatureto warm slowly to room temperature
  7. stirringstirred for 6 hours
  8. additionpoured into ice
  9. additionto the ice solution was added saturated NaHCO3 until the pH was approximately 9
  10. extractionThe aqueous solution was extracted three times with 10% MeOH in dichloromethane
  11. dry with materialdried over Magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-95b24f3ef7bc41899535782efd8ea452
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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