Formaldehyde → (S)-methyl 5-(4-chloro-2-cyanophenoxy)-2-methyl-6-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051628Notes

Reaction equation

HRID 1051628 reaction equation
C=O.[Cl:3][C:4]1[CH:36]=[CH:35][C:7]([O:8][C:9]2[C:18]([C:19]3[CH:20]=[N:21][N:22]([CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[CH:23]=3)=[CH:17][CH:16]=[C:15]3[C:10]=2[CH2:11][CH2:12][C@H:13]([CH3:34])[N:14]3[C:30]([O:32][CH3:33])=[O:31])=[C:6]([C:37]#[N:38])[CH:5]=1.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[Cl:3][C:4]1[CH:36]=[CH:35][C:7]([O:8][C:9]2[C:18]([C:19]3[CH:20]=[N:21][N:22]([CH:24]4[CH2:29][CH2:28][N:27]([CH3:39])[CH2:26][CH2:25]4)[CH:23]=3)=[CH:17][CH:16]=[C:15]3[C:10]=2[CH2:11][CH2:12][C@H:13]([CH3:34])[N:14]3[C:30]([O:32][CH3:33])=[O:31])=[C:6]([C:37]#[N:38])[CH:5]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 118076488(S)-methyl 5-(4-chloro-2-cyanophenoxy)-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 118086397(S)-methyl 5-(4-chloro-2-cyanophenoxy)-2-methyl-6-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Formaldehyde (37% aqueous solution, 0.015 mL, 0.198 mmol) was added to a solution of (S)-methyl 5-(4-chloro-2-cyanophenoxy)-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylate (0.010 g, 0.020 mmol) in methanol (1.0 mL), and the reaction mixture stirred for 2 h. The mixture was cooled to 0° C. and sodium triacetoxyborohydride (8.4 mg, 0.040 mmol) was added. The reaction mixture stirred at 0° C. and was allowed to warm to room temperature overnight. The reaction mixture was partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate and the combined organic phases were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford (S)-methyl 5-(4-chloro-2-cyanophenoxy)-2-methyl-6-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylate (0.0095 g, 92%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.06 (br d, J=6.74 Hz, 3H), 1.47-1.69 (m, 4H), 1.71-2.13 (m, 4H), 2.19 (s, 3H), 2.71-2.90 (m, 2H), 3.72 (s, 3H), 3.93-4.13 (m, 1H), 4.32-4.45 (m, 1H), 4.50-4.65 (m, 1H), 6.35-6.54 (m, 1H), 7.45-7.65 (m, 4H), 7.65-7.72 (m, 1H), 7.97 (s, 1H), 8.11 (d, J=2.64 Hz, 1H). MS (ESI, pos. ion) m/z 521 [M+H]+.

Workup

  1. stirringThe reaction mixture stirred at 0° C.
  2. temperatureto warm to room temperature overnight
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. washthe combined organic phases were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-77ab5f3a5fe747c88050829506a7740e
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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