Acetic Acid → HCID 67443204, compound

HRID 1400923Notes

Reaction equation

HRID 1400923 reaction equation
Cl.[F:2][C:3]1([F:9])[CH2:8]CCN[CH2:4]1.[CH:10]1([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]4[CH:30]=[C:31]([C:33]5[CH:38]=[CH:37][C:36]([CH:39]=O)=[CH:35][N:34]=5)[S:32][C:25]=34)=[C:19]([F:41])[CH:18]=2)=[O:15])[CH2:12][CH2:11]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].ClCCl.[CH3:63][N:64]([CH:66]=O)C>C(Cl)Cl.CO.C(Cl)(Cl)Cl>[CH:10]1([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]4[CH:30]=[C:31]([C:33]5[CH:38]=[CH:37][C:36]([CH2:39][N:64]6[CH2:66][CH2:8][C:3]([F:9])([F:2])[CH2:4][CH2:63]6)=[CH:35][N:34]=5)[S:32][C:25]=34)=[C:19]([F:41])[CH:18]=2)=[O:15])[CH2:12][CH2:11]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 27583493,3-Difluoropiperidine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 22350042dichloromethane N,N-dimethylformamideHCID 582365791-Cyclopropyl-3-(3-fluoro-4-(2-(5-formylpyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

Product 1

HCID 67443204HCID 67443204, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21584188Chloroform methanolSolvent

Procedure

3,3-Difluoropiperidine hydrochloride (0.250 g, 2.06 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 (0.100 g, 0.22 mmol) and acetic acid (0.04 mL, 0.7 mmol) in a 10:1 dichloromethane/DMF mixture (45 mL) which was stirred for 20 min at RT. Then sodium triacetoxyborohydride (0.142 g, 0.67 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 of the residue (10% methanol/chloroform) afforded title compound 316 (0.055 g, 45% yield) as a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.72 (s, 1H); 8.56 (d, J=2.7, 1H); 8.52 (d, J=5.3, 1H); 8.32 (s, 1H); 8.23 (d, J=8.0, 1H); 7.88 (d, J=8.2, 1H); 7.73 (dd, J=13.7, 1H); 7.38 (t, J=9.0, 1H); 7.22-7.18 (m, 1H); 6.65 (d, J=5.3, 1H); 6.60 (s, 1H); 3.62 (s, 2H); 135-3.30 (m, 4H?, under water peak); 2.57-2.52 (m, 1H); 2.00-1.90 (m 2H); 0.67-0.63 (m, 2H); 0.45-0.41 (m, 2H). MS (m/z): 554.6 (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-4fdcbd5bb05248058eb7ea349190ed86
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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