Acetic Acid → HCID 67444216, compound

HRID 1400922Notes

Reaction equation

HRID 1400922 reaction equation
Cl.[F:2][C:3]1([F:8])[CH2:7][CH2:6][NH:5][CH2:4]1.[CH:9]1([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][N:26]=[C:25]4[CH:29]=[C:30]([C:32]5[CH:37]=[CH:36][C:35]([CH:38]=O)=[CH:34][N:33]=5)[S:31][C:24]=34)=[C:18]([F:40])[CH:17]=2)=[O:14])[CH2:11][CH2:10]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.ClCCl.CN(C=O)C>[CH:9]1([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][N:26]=[C:25]4[CH:29]=[C:30]([C:32]5[CH:37]=[CH:36][C:35]([CH2:38][N:5]6[CH2:6][CH2:7][C:3]([F:8])([F:2])[CH2:4]6)=[CH:34][N:33]=5)[S:31][C:24]=34)=[C:18]([F:40])[CH:17]=2)=[O:14])[CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 249034823,3-Difluoropyrrolidine hydrochlorideHCID 582365791-Cyclopropyl-3-(3-fluoro-4-(2-(5-formylpyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

Product 1

HCID 67444216HCID 67444216, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

3,3-Difluoropyrollidine hydrochloride (0.200 g, 1.39 mmol) was suspended in DCM and washed with 3M NaOH. The organic phase was separated, dried over anhydrous MgSO4 and filtered into a solution of aldehyde 47 (0.090 g, 0.20 mmol) and acetic acid (0.03 mL, 0.5 mmol) in a 10:1 dichloromethane/DMF mixture (45 mL), which was stirred for 20 min at RT. Then sodium triacetoxyborohydride (0.128 g, 0.60 mmol) was added and the reaction mixture was stirred at RT for 18 h and partitioned between dichloromethane and water. The organic phase was washed with saturated aqueous NaHCO3, then dried (anhydrous MgSO4) and concentrated. Silica gel chromatography (10% methanol/ethyl acetate), of the residue followed by a second column (10% methanol/chloroform) afforded title compound 315 (0.045 g, 42% yield) as a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.74 (s, 1H); 8.57 (d, J=2.7, 1H); 8.52 (d, J=5.3, 1H); 8.34 (s, 1H); 8.26 (d, J=8.0, 1H); 7.88 (dd, J=8.2, 2.1, 1H); 7.73 (dd, J=13.7, 2.5, 1H); 7.38 (t, J=9.0, 1H); 7.22-7.19 (m, 1H); 6.65 (d, J=5.3, 1H); 6.60 (d, J=2.7, 1H); 3.71 (s, 2H); 2.92 (t, J=13.3, 2H); 2.73 (t, J=7.0, 2H); 2.57-2.52 (m, 1H); 2.27 (septet, J=7.0, 2H); 0.67-0.63 (m, 2H); 0.45-0.41 (m, 2H). MS (m/z): 540.6 (M+1).

Workup

  1. washwashed with 3M NaOH
  2. customThe organic phase was separated
  3. dry with materialdried over anhydrous MgSO4
  4. stirringthe reaction mixture was stirred at RT for 18 h
  5. custompartitioned between dichloromethane and water
  6. washThe organic phase was washed with saturated aqueous NaHCO3
  7. dry with materialdried (anhydrous MgSO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-65307fe3706f4ae88059beeac450b3b6
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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