Dimethylformamide → HCID 57525474, compound

HRID 2114483Notes

Reaction equation

HRID 2114483 reaction equation
Br[C:2]1[C:3]([CH:20]([O:23][CH3:24])[O:21][CH3:22])=[CH:4][C:5]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[N:6][CH:7]=1.C([Li])CCC.CN([CH:33]=[O:34])C.[BH4-].[Na+]>C1COCC1>[CH3:22][O:21][CH:20]([O:23][CH3:24])[C:3]1[CH:4]=[C:5]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[N:6]=[CH:7][C:2]=1[CH2:33][OH:34]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 4311764Sodium borohydrideHCID 57525467HCID 57525467, compoundHCID 178418339Butyllithium

Product 1

HCID 57525474HCID 57525474, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

5-Bromo-4-dimethoxymethyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridine (0.5 g, 1.25 mmol, 1.0 equiv) was dissolved in THF (6 mL) and cooled to −78° C. A 2.5 M solution of n-butyllithium in hexanes (0.6 mL, 1.5 mmol, 1.2 equiv) was added dropwise. The solution was stirred for 45 min, and then DMF (0.55 mL, 1.25 mmol, 1.0 equiv) was added. After 1 h, sodium borohydride (38 mg, 1.36 mmol, 1.1 equiv) was added. The mixture was allowed to warm to −40° C. for 30 min, then was quenched with satd. aq. NaHCO3 (10 mL). The mixture was extracted with chloroform (3×30 mL), and the combined extracts were dried (Na2SO4), filtered, and concentrated to afford {4-dimethoxymethyl-6-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-3-yl}-methanol as a crude mixture. This crude material (88 mg) was dissolved in THF (3 mL) and 1.0 M HCl (3 mL) was added portionwise over 3 h at 60° C. The mixture was cooled, satd. aq. NaHCO3 was added, and the mixture was extracted with chloroform (3×30 mL). The combined extracts were dried (Na2SO4), filtered, and concentrated. A portion of the resulting crude 5-hydroxymethyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridine-4-carbaldehyde (33 mg), 3,5-dimethyl-benzene-1,2-diamine (22 mg), and Na2S2O5 (36 mg) were stirred in DMF (2 mL) at 90° C. for 36 h. The reaction mixture was purified by Method 2 to afford 5.3 mg of the title compound. MS (electrospray): mass calculated for C25H34N4O2, 422.27; m/z found, 423.5 [M+H]+. 1H NMR (400 MHz, CD3OD): 8.21 (s, 1H), 7.30 (s, 1H), 7.23 (br s, 1H), 6.95 (br s, 1H), 4.68 (s, 2H), 4.34 (t, J=6.4 Hz, 2H), 2.95-2.82 (m, 2H), 2.57 (s, 3H), 2.44 (s, 3H), 2.27 (s, 3H), 2.11-1.98 (m, 2H), 1.86-1.68 (m, 4H), 1.57-1.44 (m, 2H), 1.39-1.15 (m, 5H).

Workup

  1. waitAfter 1 h
  2. temperatureto warm to −40° C. for 30 min
  3. customwas quenched with satd
  4. extractionThe mixture was extracted with chloroform (3×30 mL)
  5. dry with materialthe combined extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-8eedfb6bb6cc42d79c51bbc243c9af78
Source dataset
uspto-grants-2008_10
Patent number
US07432378B2

Reaction notes

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