Acetonitrile → HCID 86696649, compound

HRID 1774210Notes

Reaction equation

HRID 1774210 reaction equation
C(O)(C(F)(F)F)=O.[O:8]=[C:9]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:16]=2)[CH:12]=[CH:11][N:10]1CC1C=C2C(C=CN2C(OC(C)(C)C)=O)=CC=1.C([O-])(O)=O.[Na+].CC#N>ClCCl>[O:25]1[CH2:26][CH2:27][CH:22]([NH:21][C:17]2[N:16]=[C:15]([C:13]3[CH:12]=[CH:11][NH:10][C:9](=[O:8])[CH:14]=3)[CH:20]=[CH:19][N:18]=2)[CH2:23][CH2:24]1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86696709HCID 86696709, compound2×

Product 1

HCID 86696649HCID 86696649, compoundYield 28.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (2 mL) was added to a solution of tert-butyl 6-((2-oxo-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-1(2H)-yl)methyl)-1H-indole-1-carboxylate (70 mg, 0.14 mmol) in dichloromethane (3 mL) at 20° C. The mixture was stirred at room temperature for 2 hours. LC-MS showed the tert-butyl 6-((2-oxo-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-1(2H)-yl)methyl)-1H-indole-1-carboxylate had disappeared. The reaction mixture was adjusted with a saturated NaHCO3 solution to a pH of around 8-9, then extracted with dichloromethane, and dried with Na2SO4. The organic phase was evaporated, and the residue was purified with prep-HPLC (A: H2O including 0.5% NH3HCO3, B: CH3CN) to afford 141H-indol-6-yl)methyl)-4-(2-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one (11 mg, 20% yield). 1H NMR (500 MHz, (CD3)2SO) δ 11.10 (s, 1H), 8.41 (d, J=5.0 Hz, 1H), 7.92 (d, J=7.0 Hz, 1H), 7.50 (d, J=8 Hz, 1H), 7.40-7.32 (m, 3H), 7.15-7.11 (m, 2H), 7.03 (d, J=8 Hz, 1H), 6.85 (d, J=7 Hz, 1H), 6.39 (s, 1H), 5.22 (s, 2H), 3.98 (m, 1H), 3.89-3.85 (m, 2H), 3.45-3.36 (m, 2H), 1.86-1.83 (m, 2H), 1.60-1.45 (m, 2H); LCMS (ESI) m/z: 402.2 [M+H+].

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialdried with Na2SO4
  3. customThe organic phase was evaporated
  4. customthe residue was purified with prep-HPLC (A: H2O including 0.5% NH3HCO3, B

Sources & evidence

ORD record
ord-a616e650aaec4b53a76beff16b5161c3
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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