Formaldehyde → HCID 57917277, compound

HRID 69222Notes

Reaction equation

HRID 69222 reaction equation
CO.[F:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[N:11]2)=[CH:6][C:5]=1[CH2:14][C:15]1[N:19]2[N:20]=[C:21]([C:24]3[CH:25]=[N:26][N:27]([CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)[CH:28]=3)[CH:22]=[CH:23][C:18]2=[N:17][CH:16]=1.C=O.[BH3-][C:38]#N.[Na+]>C(Cl)Cl.C(O)(=O)C>[F:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[N:11]2)=[CH:6][C:5]=1[CH2:14][C:15]1[N:19]2[N:20]=[C:21]([C:24]3[CH:25]=[N:26][N:27]([CH:29]4[CH2:34][CH2:33][N:32]([CH3:38])[CH2:31][CH2:30]4)[CH:28]=3)[CH:22]=[CH:23][C:18]2=[N:17][CH:16]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 887MethanolHCID 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 57917277HCID 57917277, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To abs. MeOH (6 mL) stirred at rt were added 7-fluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline (Example 180, 104 mg, 0.243 mmol), formaldehyde (0.034 mL, 1.216 mmol) and NaBH3CN (76 mg, 1.216 mmol). The RM was then brought to pH 5-6 with addition of acetic acid and stirred at rt for 2 h. It was then taken into DCM and washed with saturated NaHCO3 sol. The organic layer was then washed with brine, dried on Na2SO4, filtered and evaporated. A purification of the crude by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH with ammonia=100:0->90:10) gave the title compound (tR 3.07 min (conditions 3), MH+=442, 1H-NMR in DMSO-d6: 8.82 (d, 1H); 8.49 (s, 1H); 8.33 (d, 1H); 8.10-8.01 (m, 3H), 7.76 (d, 1H); 7.59 (s, 1H); 7.53 (d, 1H); 7.46 (dd, 1H), 4.53 (s, 2H); 4.20-4.10 (m, 1H); 2.85 (d, 2H); 2.18 (s, 3H); 2.06-1.92 (m, 6H).

Workup

  1. washwashed with saturated NaHCO3 sol. The organic layer
  2. washwas then washed with brine
  3. customdried on Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customA purification of the crude by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH with ammonia=100:0->90:10)

Sources & evidence

ORD record
ord-788a60fbb6564c7bbfa8f4d3a35613b7
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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