Tetrahydrofurfurylamine → HCID 52914351, compound

HRID 540773Notes

Reaction equation

HRID 540773 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:6][NH2:7].[CH2:8]([N:10]1[C:14]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH:22]=O)=[CH:18][CH:17]=2)=[CH:13][C:12]([C:24]2[CH:25]=[C:26]([C:30]([NH:33][S:34]([CH2:37][C:38]([F:41])([F:40])[F:39])(=[O:36])=[O:35])([CH3:32])[CH3:31])[CH:27]=[CH:28][CH:29]=2)=[N:11]1)[CH3:9]>CN(C=O)C>[CH2:8]([N:10]1[C:14]([O:15][C:16]2[CH:17]=[CH:18][C:19]([CH2:22][NH:7][CH2:6][CH:2]3[CH2:3][CH2:4][CH2:5][O:1]3)=[CH:20][CH:21]=2)=[CH:13][C:12]([C:24]2[CH:25]=[C:26]([C:30]([NH:33][S:34]([CH2:37][C:38]([F:41])([F:39])[F:40])(=[O:35])=[O:36])([CH3:32])[CH3:31])[CH:27]=[CH:28][CH:29]=2)=[N:11]1)[CH3:9]

Participants

4

Reactant 2

HCID 253298TetrahydrofurfurylamineHCID 52913937HCID 52913937, compound

Product 1

HCID 52914351HCID 52914351, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
22 °C

Procedure

1-(tetrahydrofuran-2-yl)methanamine (12.3 mgs, 0.121 mmol, 1.2 equiv) followed by Si-bound cyanoborohydride (322 mg, 0.303 mmol, 3.0 equiv, 0.94 mmol/g) were added to N-(2-{3-[1-ethyl-5-(4-formylphenoxy)-1H-pyrazol-3-yl]phenyl}propan-2-yl)-2,2,2-trifluoroethanesulfonamide (50.0 mg, 0.101 mmol, 1 equiv) stirring in DMF (with 0.05% acetic acid v:v, 0.5 mL). The resulting mixture was stirred at 22° C. for 16 hours then filtered through a 0.45 micron nylon syringe filter and flushed with methanol. The filtrate was purified by reversed phase HPLC (0-95% acetonitrile:water with 0.025% TFA v:v). Pure fractions were identified, combined, basified with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The drying agent was filtered away and the filtrate was concentrated in vacuo to give N-(2-{3-[1-ethyl-5-(4-{[(tetrahydrofuran-2-ylmethyl)amino]methyl}phenoxy)-1H-pyrazol-3-yl]phenyl}propan-2-yl)-2,2,2-trifluoroethanesulfonamide. Calc'd (M+1) 581.2. Found: 581.2

Workup

  1. filtrationthen filtered through a 0.45 micron nylon syringe
  2. filtrationfilter
  3. customflushed with methanol
  4. customThe filtrate was purified by reversed phase HPLC (0-95% acetonitrile:water with 0.025% TFA v:v)
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe drying agent was filtered away
  9. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-3611655998404d96bf508fb5810efe9f
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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