Sodium Hydroxide → HCID 89996074, compound

HRID 1480844Notes

Reaction equation

HRID 1480844 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.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[Cl:28][C:29]1[C:34]2[N:35]=C(S(C)(=O)=O)[N:37]=[CH:38][C:33]=2[CH:32]=[C:31]([CH:43]2[CH2:45][CH2:44]2)[N:30]=1.[OH-].[Na+]>C1COCC1.CO>[Cl:28][C:29]1[C:34]2[N:35]=[C:16]([NH:15][C:4]3[CH:5]=[CH:6][C:7]([C:9]4[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=4)=[CH:8][C:3]=3[O:2][CH3:1])[N:37]=[CH:38][C:33]=2[CH:32]=[C:31]([CH:43]2[CH2:44][CH2:45]2)[N:30]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 89996145HCID 89996145, compoundHCID 89996185HCID 89996185, compound

Product 1

HCID 89996074HCID 89996074, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

N-(2-Methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)formamide (Preparation 56, 50 mg 0.21 mmole) was stirred in THF (1 mL). Sodium hexamethyldisilazide (0.25 mL of 1M solution in THF) was added and the reaction stirred at room temperature for 20 minutes. 8-Chloro-6-cyclopropyl-2-(methylsulfonyl)pyrido[3,4-d]pyrimidine (Preparation 179, 80 mg, 0.28 mmole) was added as a suspension in THF (1.5 mL) and the reaction was stirred at room temperature for 80 minutes. Methanol (1 mL) and 1M sodium hydroxide solution (1 mL) were added to the reaction and stirred for 55 minutes. The solvents were then concentrated in vacuo. The residue was partitioned between chloroform (10 mL) and water (10 mL). The layers were separated and the aqueous was again extracted with chloroform. The combined organic layers were dried and concentrated in vacuo. The residue was purified using preparative TLC eluting with 1:1 acetone:cyclohexane to afford the title compound (41 mg 44%).

Workup

  1. stirringthe reaction was stirred at room temperature for 80 minutes
  2. stirringstirred for 55 minutes
  3. concentrationThe solvents were then concentrated in vacuo
  4. customThe residue was partitioned between chloroform (10 mL) and water (10 mL)
  5. customThe layers were separated
  6. extractionthe aqueous was again extracted with chloroform
  7. customThe combined organic layers were dried
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified
  10. washeluting with 1:1 acetone

Sources & evidence

ORD record
ord-1bd467a0105f480c9c358eda5028cc35
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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