Formaldehyde → HCID 118086402, compound

HRID 1051655Notes

Reaction equation

HRID 1051655 reaction equation
[NH:1]1[CH2:4][CH:3]([N:5]2[CH:9]=[C:8]([C:10]3[C:11]([O:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)=[C:12]4[C:17](=[CH:18][CH:19]=3)[N:16]([C:20]([O:22][CH3:23])=[O:21])[C@@H:15]([CH3:24])[CH2:14][CH2:13]4)[CH:7]=[N:6]2)[CH2:2]1.C=O.[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[F:32][C:29]1[CH:28]=[CH:27][C:26]([O:25][C:11]2[C:10]([C:8]3[CH:7]=[N:6][N:5]([CH:3]4[CH2:2][N:1]([CH3:35])[CH2:4]4)[CH:9]=3)=[CH:19][CH:18]=[C:17]3[C:12]=2[CH2:13][CH2:14][C@H:15]([CH3:24])[N:16]3[C:20]([O:22][CH3:23])=[O:21])=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 118086400HCID 118086400, compound

Product 1

HCID 118086402HCID 118086402, compoundYield 79.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl (S)-6-(1-(azetidin-3-yl)-1H-pyrazol-4-yl)-5-(4-fluorophenoxy)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (105 mg, 0.241 mmol) was dissolved in methanol and formaldehyde (179 μL, 2.41 mmol) was added. The reaction was stirred for 4 h at ambient temperature and then cooled to 0° C. Sodium triacetoxyborohydride (0.102 g, 0.481 mmol) was added and the reaction was slowly warmed to ambient temperature. After 16 h the reaction was complete, and the reaction mixture was partitioned between ethyl acetate and water. The aqueous phase was separated and extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford methyl (S)-5-(4-fluorophenoxy)-2-methyl-6-(1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylate (0.086 g, 79%) as a pale orange oil. 1H NMR (300 MHz, CDCl3) δ ppm 1.13 (d, J=6.45 Hz, 3H) 1.18-1.20 (m, 1H) 1.20-1.33 (m, 1H) 1.55 (br dd, J=13.34, 5.42 Hz, 1H) 1.94-2.18 (m, 4H) 2.22-2.49 (m, 1H) 2.49-2.69 (m, 1H) 3.81 (s, 3H) 4.26 (br s, 1H) 4.61-4.89 (m, 2H) 5.13-5.32 (m, 1H) 6.63-6.82 (m, 2H) 6.83-7.01 (m, 2H) 7.40 (d, J=8.79 Hz, 1H) 7.54-7.67 (m, 2H) 7.79-8.02 (m, 1H). MS (ESI, pos. ion) m/z 451 [M+H]+.

Workup

  1. temperaturecooled to 0° C
  2. temperaturethe reaction was slowly warmed to ambient temperature
  3. waitAfter 16 h the reaction was complete
  4. customthe reaction mixture was partitioned between ethyl acetate and water
  5. customThe aqueous phase was separated
  6. extractionextracted with ethyl acetate
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-303084e9efde49a4bf61fcdc0a399254
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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