Sodium hydride → HCID 89995975, compound

HRID 1480778Notes

Reaction equation

HRID 1480778 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[CH:6]=[CH:5][C:4]=1[NH:15][CH:16]=O.[H-].[Na+].[CH3:20][C:21]1[N:34]=[C:33]([NH:35][CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C:24]2[N:25]=C(S(C)(=O)=O)[N:27]=[CH:28][C:23]=2[CH:22]=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[CH:6]=[CH:5][C:4]=1[NH:15][C:16]1[N:27]=[CH:28][C:23]2[CH:22]=[C:21]([CH3:20])[N:34]=[C:33]([NH:35][CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C:24]=2[N:25]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 89996181HCID 89996181, compoundHCID 89996185HCID 89996185, compound

Product 1

HCID 89995975HCID 89995975, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (0° C.) suspension of N-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)formamide (Preparation 56, 8.5 mg, 0.037 mmol) in THF (1 mL) was added NaH (60% dispersion in oil, 2.4 mg, 0.059 mmol). The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was cooled to 0° C. and 6-methyl-2-(methysulfonyl)-N-neopentylpyrido[3,4-d]pyrimidin-8-amine (Preparation 54, 12.5 mg, 0.040 mmol) in THF (1 mL) was added. The reaction mixture was stirred for 5 hours, whilst slowly warming to room temperature. The reaction mixture was concentrated in vacuo. The residue was partitioned between EtOAc (30 mL) and water (30 mL). The aqueous layer was re-extracted with EtOAc and DCM (25 mL). The combined organic layers were washed with water (25 mL) and brine (25 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 50-100% EtOAc in cyclohexane. The residue was purified by passage through a SCX-2 cartridge eluting with 100% MeOH-1M NH3 in MeOH to give the title compound (5.0 mg, 32%).

Workup

  1. temperatureTo a cooled
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. stirringThe reaction mixture was stirred for 5 hours
  4. temperaturewhilst slowly warming to room temperature
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customThe residue was partitioned between EtOAc (30 mL) and water (30 mL)
  7. extractionThe aqueous layer was re-extracted with EtOAc and DCM (25 mL)
  8. washThe combined organic layers were washed with water (25 mL) and brine (25 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel column chromatography
  12. washeluting with 50-100% EtOAc in cyclohexane
  13. customThe residue was purified by passage through a SCX-2 cartridge
  14. washeluting with 100% MeOH-1M NH3 in MeOH

Sources & evidence

ORD record
ord-73359052f2774c79a398ece4ed9322c8
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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