Methanol → HCID 73056521, compound

HRID 2284424Notes

Reaction equation

HRID 2284424 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[CH:8]=[C:9]([C:13]3[CH:22]=[N:21][C:20]4[C:19]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)=[N:18][C:17]([C:29]5[CH:30]=[N:31][C:32]([NH:35]C(=O)OC(C)(C)C)=[N:33][CH:34]=5)=[N:16][C:15]=4[CH:14]=3)[CH:10]=[CH:11][CH:12]=2)=[O:5])[CH2:3][CH2:2]1.C(Cl)Cl.FC(F)(F)C(O)=O.CO>C(Cl)(Cl)Cl>[NH2:35][C:32]1[N:31]=[CH:30][C:29]([C:17]2[N:18]=[C:19]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[C:20]3[N:21]=[CH:22][C:13]([C:9]4[CH:8]=[C:7]([NH:6][C:4]([CH:1]5[CH2:2][CH2:3]5)=[O:5])[CH:12]=[CH:11][CH:10]=4)=[CH:14][C:15]=3[N:16]=2)=[CH:34][N:33]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86710187HCID 86710187, compound

Product 1

HCID 73056521HCID 73056521, compoundYield 82.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

To a 50 mL round bottom flask, tert-butyl (5-(7-(3-(cyclopropanecarboxamido)phenyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-yl)carbamate (0.15 g, 0.00026 mol) and DCM (10 mL) were added and then cooled to 0° C. To the same reaction flask, trifluoroacetic acid (0.12 g, 0.00104 mol) was added at 0° C. and the reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was quenched with saturated sodium bicarbonate solution and extracted with 10% methanol in chloroform. 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 3-4% methanol in chloroform. The obtained solid was washed diethyl ether, filtered and dried under vacuum to afford the title compound (0.1 g, 81%). 1H NMR (400 MHz, DMSO-d6): δ 10.44 (s, 1H), 9.23 (s, 2H), 9.04 (d, J=2.4 Hz, 1H), 8.27 (d, J=2.4 Hz, 1H), 8.23 (s, 1H), 7.68-7.50 (m, 3H), 7.24 (br s, 2H), 4.55 (br s, 4H), 3.86 (d, J=4.0 Hz, 4H), 1.85-1.83 (m, 1H), 0.87-0.85 (m, 4H): LC-MS (ESI): Calculated mass: 468.2; Observed mass [M+H]+: 469.1. (RT=0.35 min).

Workup

  1. customThe reaction mixture was quenched with saturated sodium bicarbonate solution
  2. extractionextracted with 10% methanol in chloroform
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto provide the crude product
  7. washThe obtained solid was washed diethyl ether
  8. filtrationfiltered
  9. customdried under vacuum

Sources & evidence

ORD record
ord-381e5f00ed3746a597091fa7aa33c95b
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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