Acetic Acid → HCID 67444139, compound

HRID 1400962Notes

Reaction equation

HRID 1400962 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27](C=O)=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:32])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.[OH:33][CH:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.[C:40](O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:40][N:37]6[CH2:38][CH2:39][CH:34]([OH:33])[CH2:35][CH2:36]6)=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:32])[CH:9]=2)=[O:6])[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 79341Piperidin-4-ol2×HCID 5049666Sodium triacetoxyborohydride2×HCID 582365791-Cyclopropyl-3-(3-fluoro-4-(2-(5-formylpyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

Product 1

HCID 67444139HCID 67444139, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of the aldehyde 47 (0.3 g, 0.669 mmol) in a mixture of DCM (9 mL) and DMF (3 mL) were added 4-hydroxypiperidine (0.135 g, 1.34 mmol) and acetic acid (0.08 mL, 1.34 mmol) at RT. The reaction mixture was stirred for 30 min; NaBH(OAc)3 (0.425 g, 2.00 mmol) was added and the reaction mixture was stirred overnight. More 4-hydroxypiperidine (0.135 g, 1.34 mmol) and NaBH(OAc)3 (0.425 g, 2.00 mmol) were added to the reaction mixture that was stirred at room temperature for 4 hr, then quenched by addition of saturated NaHCO3 solution and extracted with DCM/MeOH. The organic layer was washed with brine and dried over MgSO4 and concentrated. The crude product was purified by flash chromatography on silica gel (DCM/MeOH:90/10 to 75/25) then triturated with MeOH to afford title compound 599 (0.17 g, 48% yield) as a brown solid. 1H NMR (300 MHz, DMSO-d6) δ (ppm): 8.71 (s, 1H), 8.56-8.53 (m, 1H), 8.52 (d, J=5.4 Hz, 1H), 8.31 (s, 1H), 8.23 (d, J=8.1 Hz, 1H), 7.85 (dd, J=8.4, 2.4 Hz, 1H), 7.73 (dd, J=13.5, 2.4 Hz, 1H), 7.38 (t, J=9.0 Hz, 1H), 7.24-7.18 (m, 1H), 6.65 (d, J=5.4 Hz, 1H), 6.56 (d, J=2.1 Hz, 1H), 4.58 (d, J=4.2 Hz, 1H), 3.54 (s, 2H), 3.50-3.40 (m, 1H), 2.75-2.65 (m, 2H), 2.60-2.50 (m, 1H), 2.19-2.05 (m, 2H), 1.80-1.65 (m, 2H), 1.50-1.35 (m, 2H), 0.71-0.64 (m, 2H), 0.48-0.40 (m, 2H).

Workup

  1. stirringthe reaction mixture was stirred overnight
  2. stirringwas stirred at room temperature for 4 hr
  3. customquenched by addition of saturated NaHCO3 solution
  4. extractionextracted with DCM/MeOH
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography on silica gel (DCM/MeOH:90/10 to 75/25)
  9. customthen triturated with MeOH

Sources & evidence

ORD record
ord-aa34b5b395eb41d7b310d4c73b2b27db
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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