Sodium hydride → HCID 60208932, compound

HRID 225925Notes

Reaction equation

HRID 225925 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([N:12]([CH3:24])[CH2:13][C:14]2[N:15]([CH3:23])[C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:11])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:28][C:29](OC)([O:31]C)[CH3:30]>CN(C=O)C>[CH3:24][N:12]([CH2:13][C:14]1[N:15]([CH3:23])[C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10](=[O:11])/[CH:9]=[CH:8]/[C:5]1[CH:6]=[N:7][C:2]([NH:1][CH2:28][C:29](=[O:31])[CH3:30])=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 671751-Bromo-2,2-dimethoxypropaneHCID 52877203-(6-Aminopyridin-3-Yl)-N-Methyl-N-((1-Methyl-1h-Indol-2-Yl)Methyl)Acrylamide

Product 1

HCID 60208932HCID 60208932, compoundYield 9.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (E)-3-(6-aminopyridin-3-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide (0.12 g, 0.32 mmol), from Example 1, in DMF (1 mL) was added NaH (14 mg. 60% dispersion in oil, 0.35 mmol) and 1-bromo-2,2-dimethoxy-propane (0.05 mL, 0.37 mmol). After 18 h at RT, the reaction was complete by TLC analysis. The solvent was removed under vacuum and the residue was purified by reverse phase preparative HPLC (YMC CombiPrep® ODS-A, 10% to 90% CH3CN/H2O+0.1% TFA) to give the title compound (11.6 mg) as a pale yellow oil: 1H NMR (400 MHz, MeOH-d4, 2:1 mixture of rotamers, minor rotamer in italics) δ 9.28 and 9.22 (s, 1 H), 8.60 and 8.52 (s, 1 H). 8.25 and 8.15 (d, 1 H), 7.68 (d, J=16 Hz, 1 H), 7.50 (m, 1 H), 7.35 (m, 3 H), 7.15 (m, 1 H), 7.02 (m, 1 H), 6.55 and 6.25 (s, 1 H), 5.05 and 4.95 (s, 2 H), 3.72 and 3.68 (s, 3 H), 3.50 and 3.48 (s, 3 H), 3.35 (s, 2 H), 3.15 and 3.10 (s, 3 H). MS (ES+) m/e 376.3 (M+H)+. Unreacted (E)-3-(6-aminopyridin-3-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide (68 mg) was also recovered.

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue was purified by reverse phase preparative HPLC (YMC CombiPrep® ODS-A, 10% to 90% CH3CN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-17d5a8271ee64631b44d755a55cbfe35
Source dataset
uspto-grants-2009_07
Patent number
US07557125B2

Reaction notes

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