Tetrahydro-4H-pyran-4-ol → HCID 57829823, compound

HRID 1855418Notes

Reaction equation

HRID 1855418 reaction equation
[Na].Cl[C:3]1[CH:8]=[C:7]([CH3:9])[N:6]=[C:5]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]3)=[C:13]([O:23][CH3:24])[CH:12]=2)[N:4]=1.[O:25]1[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]1>>[CH3:24][O:23][C:13]1[CH:12]=[C:11]([NH:10][C:5]2[N:6]=[C:7]([CH3:9])[CH:8]=[C:3]([O:31][CH:28]3[CH2:29][CH2:30][O:25][CH2:26][CH2:27]3)[N:4]=2)[CH:16]=[CH:15][C:14]=1[N:17]1[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]1

Participants

4

Reactant 3

HCID 74956Tetrahydro-4H-pyran-4-olHCID 5360545SodiumHCID 57829826HCID 57829826, compound

Product 1

HCID 57829823HCID 57829823, compoundYield 11%

Conditions

Temperature
100 °C

Procedure

Sodium (10 mg, 0.45 mmol) was dissolved under stirring and heating (100° C. for 3 hours) under an atmosphere of nitrogen in tetrahydro-4H-pyran-4-ol (0.99 mL). (4-Chloro-6-methyl-pyrimidin-2-yl)-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine (99 mg, 0.3 mmol) was added and the suspension was heated to 100° C. for 2 hours. The solvent was evaporated under reduced pressure and the residue was taken up in water and extracted twice with diethyl ether. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated under reduced pressure to dryness. The residue was purified by reversed preparative HPLC using acetonitril/water (0.1% formic acid) to yield the title compound as a white solid (13 mg, 11%). MS ISP (m/e): 396.2 (100) [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.65 (s, 1H), 7.62 (s, 1H), 7.17 (d, 1H), 7.15 (s, 1H), 7.13 (d, 1H), 6.87 (s, 1H), 6.12 (s, 1H), 5.30 (m, 1H), 3.98 (m, 2H), 3.86 (s, 3H), 3.62 (m, 2H), 2.36 (s, 3H), 2.31 (s, 3H), 2.04 (m, 2H), 1.84 (m, 2H).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. extractionextracted twice with diethyl ether
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure to dryness
  7. customThe residue was purified by reversed preparative HPLC

Sources & evidence

ORD record
ord-87100b0b07a74de395815bff6d150aa2
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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