Acetic Acid → 6-[6-(1-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-piperidin-4-yl}-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-7-fluoro-quinoline

HRID 69188Notes

Reaction equation

HRID 69188 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[CH2:12][C:13]1[N:17]2[N:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)[CH:26]=3)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1.[Si:33]([O:40][CH2:41][CH:42]=O)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34].[BH3-]C#N.[Na+].CC(O)=O>CO.C(Cl)Cl>[C:36]([Si:33]([CH3:35])([CH3:34])[O:40][CH2:41][CH2:42][N:30]1[CH2:31][CH2:32][CH:27]([N:25]2[CH:26]=[C:22]([C:19]3[CH:20]=[CH:21][C:16]4[N:17]([C:13]([CH2:12][C:3]5[CH:4]=[C:5]6[C:10](=[CH:11][C:2]=5[F:1])[N:9]=[CH:8][CH:7]=[CH:6]6)=[CH:14][N:15]=4)[N:18]=3)[CH:23]=[N:24]2)[CH2:28][CH2:29]1)([CH3:39])([CH3:38])[CH3:37]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 579174297-fluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

Product 1

HCID 686342406-[6-(1-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-piperidin-4-yl}-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-7-fluoro-quinoline

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 7-fluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline (Example 180, 70 mg, 0.164 mmol), tert-butyldimethylsilyloxy-acetaldehyde (47 μL, 0.246 mmol) and NaBH3CN (52 mg, 0.246 mmol) in MeOH (2 mL) was stirred at rt for 2 h. The pH was then adjusted to 5-6 with AcOH and the RM was stirred at rt for 2 h more. The mixture was diluted with DCM and washed with NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated to afford the title compound as a foam (tR 4.27 min (conditions 3), MH+=586.1).

Workup

  1. stirringthe RM was stirred at rt for 2 h more
  2. washwashed with NaHCO3 and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-e35c972c920149f49fe323473e220e2c
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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