Sodium hydride → HCID 86696703, compound

HRID 1774203Notes

Reaction equation

HRID 1774203 reaction equation
[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[N:15]=[C:14]([C:16]3[CH:21]=[CH:20][NH:19][C:18](=[O:22])[CH:17]=3)[CH:13]=[CH:12][N:11]=2)[CH2:5][CH2:4]1.CS(O[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([F:37])[CH:31]=1)(=O)=O>CN(C=O)C>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][CH2:28][N:19]2[CH:20]=[CH:21][C:16]([C:14]3[CH:13]=[CH:12][N:11]=[C:10]([NH:9][CH:6]4[CH2:7][CH2:8][O:3][CH2:4][CH2:5]4)[N:15]=3)=[CH:17][C:18]2=[O:22])=[CH:31][C:32]=1[F:37]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86696649HCID 86696649, compoundHCID 86696704HCID 86696704, compound

Product 1

HCID 86696703HCID 86696703, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

NaH (11.1 mg, 0.277 mmol; 60% oil dispersion) neat as a solid was added to a stirred suspension of 4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (75.4 mg, 0.277 mmol) in DMF (700 μL) at room temperature under nitrogen. After 15 minutes, a clear solution had formed. A solution of 4-chloro-3-fluorophenethyl methanesulfonate (105 mg, 0.416 mmol) in of DMF (700 μL) was then added dropwise. After stirring overnight, the reaction was quenched by addition of saturated ammonium chloride solution (1 mL). The mixture was partitioned between ethyl acetate (30 mL) and water (30 mL). The organics were isolated and washed with water (3×30 mL) and with brine (30 mL). The organics were isolated, dried (MgSO4), filtered and concentrated. The crude product was loaded onto a Biotage 12M column with 2.5/97.5 methanol/ethyl acetate and eluted. The undesired O-alkylated product eluted first and was not collected. Product containing fractions then eluted and were pooled and concentrated to an oil that eventually solidified, 1-(4-chloro-3-fluorophenethyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (20 mg, 17%). 1H NMR (400 MHz, CDCl3) δ 8.38 (d, 1H), 7.30 (dd, 1H), 7.18 (br s, 1H), 7.02 (d, 1H), 6.98 (dd, 1H), 6.90 (m, 2H), 6.66 (dd, 1H), 5.17 (br d, 1H), 4.16 (t, 2H), 4.12 (m, 1H), 4.00 (m, 2H), 3.57 (m, 2H), 3.08 (t, 2H), 2.06 (m, 2H), 1.58 (m, 2H); m/z (APCI-pos) M+1=430.1.

Workup

  1. customa clear solution had formed
  2. customthe reaction was quenched by addition of saturated ammonium chloride solution (1 mL)
  3. customThe mixture was partitioned between ethyl acetate (30 mL) and water (30 mL)
  4. customThe organics were isolated
  5. washwashed with water (3×30 mL) and with brine (30 mL)
  6. customThe organics were isolated
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washeluted
  11. washThe undesired O-alkylated product eluted first
  12. customwas not collected
  13. additionProduct containing fractions
  14. washthen eluted
  15. concentrationconcentrated to an oil that

Sources & evidence

ORD record
ord-6ffd81f486fc47cc833c674fcd9b1d9f
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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