Formaldehyde → HCID 70872537, compound

HRID 1616520Notes

Reaction equation

HRID 1616520 reaction equation
Cl.[CH2:2]([N:4]([CH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)[C:5]1[C:6]([CH3:39])=[C:7]([CH:24]=[C:25]([C:27]2[CH:28]=[N:29][C:30]([N:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[CH:31][CH:32]=2)[CH:26]=1)[C:8]([NH:10][CH2:11][C:12]1[C:13](=[O:23])[NH:14][C:15]([CH3:22])=[C:16]([F:21])[C:17]=1[CH:18]([CH3:20])[CH3:19])=[O:9])[CH3:3].C=[O:47].O.[C:49]([BH3-])#N.[Na+]>CO>[CH:44]([OH:43])=[O:47].[CH2:2]([N:4]([CH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)[C:5]1[C:6]([CH3:39])=[C:7]([CH:24]=[C:25]([C:27]2[CH:28]=[N:29][C:30]([N:33]3[CH2:38][CH2:37][N:36]([CH3:49])[CH2:35][CH2:34]3)=[CH:31][CH:32]=2)[CH:26]=1)[C:8]([NH:10][CH2:11][C:12]1[C:13](=[O:23])[NH:14][C:15]([CH3:22])=[C:16]([F:21])[C:17]=1[CH:18]([CH3:20])[CH3:19])=[O:9])[CH3:3]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 70872708HCID 70872708, compound

Product 1

HCID 70872537HCID 70872537, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-N-((5-fluoro-4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(6-(piperazin-1-yl)pyridin-3-yl)benzamide hydrochloride (160 mg, 0.25 mmol) in methanol (2 mL) at 0° C. was added 35% solution of formaldehyde in water (0.196 mL, 2.495 mmol). After stirring for 20 min, sodium cyanoborohydride (31.4 mg, 0.499 mmol) was added. After 1.5 h at 0° C., the reaction was quenched with water (3 mL), cooling bath was removed, mixture was stirred for 10 min. Then DCM (10 mL) and saturated aq NaHCO3 (1 mL) were added. The organic layer was separated and the aqueous layer was extracted with DCM (2×15 mL) and the combined organic extracts were dried over sodium sulfate, filtered and concentrated. The product was purified by reverse phase HPLC/MS (ACN—H2O, 0.5% formic acid) to afford 3-(Ethyl(tetrahydro-2H-pyran-4-yl)amino)-N-((5-fluoro-4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)benzamide formate (31 mg, 0.047 mmol, 19% yield) as a colorless glassy film.

Workup

  1. waitAfter 1.5 h at 0° C.
  2. customthe reaction was quenched with water (3 mL)
  3. temperaturecooling bath
  4. customwas removed
  5. stirringmixture was stirred for 10 min
  6. additionThen DCM (10 mL) and saturated aq NaHCO3 (1 mL) were added
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with DCM (2×15 mL)
  9. dry with materialthe combined organic extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe product was purified by reverse phase HPLC/MS (ACN—H2O, 0.5% formic acid)

Sources & evidence

ORD record
ord-7e6d82b633a44115bd8257e83149f94f
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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