Trimethyl orthoformate → HCID 69375477, compound

HRID 861096Notes

Reaction equation

HRID 861096 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]2[NH:12][N:11]=[C:10]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)[C:9]=2[C:20]2[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=2)[CH2:4][CH2:3]1.C(OC)(OC)OC.[S:33]1[CH:37]=[CH:36][N:35]=[C:34]1[CH:38]=O.[OH-].[Na+]>CO>[CH3:38][C:34]1[S:33][CH:37]=[C:36]([N:2]2[CH2:3][CH2:4][CH:5]([C:8]3[NH:12][N:11]=[C:10]([C:13]4[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=4)[C:9]=3[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)[CH2:6][CH2:7]2)[N:35]=1

Participants

6

Reactant 4

HCID 9005Trimethyl orthoformateHCID 14798Sodium HydroxideHCID 27349031,3-Thiazole-2-carbaldehydeHCID 22037252HCID 22037252, compound

Product 1

HCID 69375477HCID 69375477, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 5-(4-piperidyl)-4-(4-pyridyl)-3-(4-chlorophenyl)pyrazole hydrochloride (Example C-74) in 12 mL of MeOH was added trimethyl orthoformate (2.6 g, 24.4 mmol) and 2-thiazolecarboxaldehyde (1.4 g, 12.2 mmol). The suspension was stirred at room temperature for 2 h. To this mixture was added NaCNBH (1.5 g, 24.4 mmol) and the resulting suspension was stirred at room temperature for 7 days. The mixture was poured onto 2.5 N NaOH and was extracted with ethyl acetate (2×100 mL). The combined extracts were washed with brine (1×100 mL), dried over Na2SO4, filtered and concentrated to leave a solid. This solid was triturated with ether and filtered to afford the title compound: MS (M+H): 436 (base peak).

Workup

  1. additionTo this mixture was added NaCNBH (1.5 g, 24.4 mmol)
  2. stirringthe resulting suspension was stirred at room temperature for 7 days
  3. extractionwas extracted with ethyl acetate (2×100 mL)
  4. washThe combined extracts were washed with brine (1×100 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto leave a solid
  9. customThis solid was triturated with ether
  10. filtrationfiltered

Sources & evidence

ORD record
ord-909e15dbb46c46d0ac467c5a8e756018
Source dataset
uspto-grants-2006_12
Patent number
US07153959B2

Reaction notes

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