Methanol → HCID 72792433, compound

HRID 2284408Notes

Reaction equation

HRID 2284408 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[N:16][C:15]3[C:14]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[N:13][C:12]([C:24]4[CH:25]=[N:26][C:27]([NH:30]C(=O)OC(C)(C)C)=[N:28][CH:29]=4)=[N:11][C:10]=3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C(Cl)Cl.F[C:42](F)(F)[C:43](O)=[O:44].CO>C(Cl)(Cl)Cl>[NH2:30][C:27]1[N:28]=[CH:29][C:24]([C:12]2[N:13]=[C:14]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:15]3[N:16]=[CH:17][C:8]([C:4]4[CH:3]=[C:2]([NH:1][C:43](=[O:44])[CH3:42])[CH:7]=[CH:6][CH:5]=4)=[CH:9][C:10]=3[N:11]=2)=[CH:25][N:26]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86710176HCID 86710176, compound

Product 1

HCID 72792433HCID 72792433, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

To a 250 mL round bottom flask, tert-butyl (5-(7-(3-aminophenyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-yl)carbamate (1.6 g, 0.0029 mol) and DCM (160 mL) were added and the flask cooled to 0° C. To the reaction flask, trifluoroacetic acid (16 mL, 10% volume) was added at 0° C. and the reaction mixture was stirred at room temperature for 3 hours. The volatiles were evaporated under reduced pressure and methanol was added to provide a solid. The solid was collected by filtration. The solid was suspended into water and basified with saturated sodium bicarbonate solution. The reaction mixture was extracted with chloroform (3×200 mL). The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide the crude product. The crude product was subjected to flash column chromatography using 4% methanol in chloroform. The obtained solid was washed with methanol and diethyl ether, filtered and dried under vacuum to afford the title compound as off-white solid (0.900 g, 69%). 1H NMR (400 MHz, DMSO-d6): δ 10.18 (s, 1H), 9.22 (s, 2H), 9.02 (d, J=2.0 Hz, 1H), 8.26 (d, J=2.0 Hz, 1H), 8.19 (s, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.63 (d, J=8.0 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.24 (s, 2H), 4.55 (br s, 4H), 3.87 (t, J=4.4 Hz, 4H), 2.12 (s, 3H). LC-MS (ESI): Calculated mass: 442.2; Observed mass [M+H]+: 443.1. (RT=0.18 min).

Workup

  1. customThe volatiles were evaporated under reduced pressure and methanol
  2. additionwas added
  3. customto provide a solid
  4. filtrationThe solid was collected by filtration
  5. extractionThe reaction mixture was extracted with chloroform (3×200 mL)
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto provide the crude product
  10. washThe obtained solid was washed with methanol and diethyl ether
  11. filtrationfiltered
  12. customdried under vacuum

Sources & evidence

ORD record
ord-1b15816c3ca2476491d797a5d34df5d7
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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