Formaldehyde → HCID 73291876, compound

HRID 1398038Notes

Reaction equation

HRID 1398038 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:19]=[CH:18][CH:17]=[CH:16][C:14]=3[NH2:15])[N:11]=[C:10]([CH:20]3[CH2:25][C:24]([CH3:27])([CH3:26])[O:23][C:22]([CH3:29])([CH3:28])[CH2:21]3)[CH:9]=2)=[CH:4][CH:3]=1.C=O.[C:32]([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>C1COCC1.C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:19]=[CH:18][CH:17]=[CH:16][C:14]=3[NH:15][CH3:32])[N:11]=[C:10]([CH:20]3[CH2:25][C:24]([CH3:27])([CH3:26])[O:23][C:22]([CH3:29])([CH3:28])[CH2:21]3)[CH:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 73292040HCID 73292040, compound

Product 1

HCID 73291876HCID 73291876, compoundYield 33.8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(5-(4-chlorophenyl)-3-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)-1H-pyrazol-1-yl)aniline (Example 62) (25 mg, 0.06 mmol, 1 eq) in THF (2 mL) was added formaldehyde (13.64 of a 37% aqueous solution, 0.18 mmol, 3 eq). After 15 min, acetic acid (0.1 mL) and sodium cyanoborohydride (12 mg, 0.18 mmol, 3 eq) were added and the solution stirred 5 hrs. Aqueous saturated NaHCO3 was added, the solution extracted with DCM, the organics combined, dried over MgSO4 and concentrated. Purification by RP-HPLC, eluting with a linear gradient of 20%-100% CH3CN in 0.1% TFA/H2O followed by freebasing with aqueous MP-carbonate resin in DCM and concentration gave 8.6 mg (32%) the title compound.

Workup

  1. extractionthe solution extracted with DCM
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customPurification by RP-HPLC
  5. washeluting with a linear gradient of 20%-100% CH3CN in 0.1% TFA/H2O
  6. concentrationby freebasing with aqueous MP-carbonate resin in DCM and concentration

Sources & evidence

ORD record
ord-a4636eb2fe5546cdb30bfd2129b3cdb0
Source dataset
uspto-grants-2014_12
Patent number
US08901314B2

Reaction notes

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