Dimethylamine → HCID 24953754, compound

HRID 1801584Notes

Reaction equation

HRID 1801584 reaction equation
Cl[C:2]1[CH:27]=[CH:26][C:5]([C:6]([NH:8][C:9]2[CH:14]=[C:13]([CH2:15][NH:16][C@@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])[CH:12]=[CH:11][C:10]=2[Cl:25])=[O:7])=[CH:4][N:3]=1.[CH3:28][NH:29][CH3:30]>C1COCC1>[Cl:25][C:10]1[CH:11]=[CH:12][C:13]([CH2:15][NH:16][C@@H:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH3:18])=[CH:14][C:9]=1[NH:8][C:6](=[O:7])[C:5]1[CH:26]=[CH:27][C:2]([N:29]([CH3:30])[CH3:28])=[N:3][CH:4]=1

Participants

4

Reactant 2

HCID 674DimethylamineHCID 24953050HCID 24953050, compound

Product 1

HCID 24953754HCID 24953754, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-6-chloro-N-(2-chloro-5-((1-phenylethylamino)methyl)phenyl)nicotinamide 48 (0.175 g, 0.44 mmol) in THF (3 mL) at 0° C. was added dimethylamine (5.0 mL, 153 mmol). The reaction mixture was warmed to room temperature, stirred for 20 h, quenched with saturated NaHCO3, and diluted with EtOAc. The organic phase was washed with saturated NaHCO3 (1×), brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 50% to 100% EtOAc in hexanes) gave (R)—N-(2-chloro-5-((1-phenylethylamino)methyl)phenyl)-6-(dimethylamino)nicotinamide 49 (0.118 g, 66% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.37 (d, J=6.5 Hz, 3H), 3.19 (s, 6H), 3.60 (d, J=13.5 Hz, 1H), 3.66 (d, J=13.5 Hz, 1H), 3.81 (q, J=6.6 Hz, 3H), 6.57 (d, J=8.6 Hz, 1H), 7.00 (dd, J=8.2, 2.2 Hz, 1H), 7.25-7.37 (m, 7H), 8.00 (dd, J=9.0, 2.5 Hz, 1H), 8.27 (s, 1H), 8.49 (d, J=2.0 Hz, 1H), 8.76 (d, J=2.2 Hz, 1H). Mass spectrum: calculated for C23H25ClN4O 408.2. found 409.2 (M++1).

Workup

  1. customquenched with saturated NaHCO3
  2. additiondiluted with EtOAc
  3. washThe organic phase was washed with saturated NaHCO3 (1×), brine (1×)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography on silica gel (eluted with 50% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-48871b83a77d438b9f565f5197b6d96b
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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