Sodium hydride → N-(1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(prop-1-en-2-yl)benzamide

HRID 1478909Notes

Reaction equation

HRID 1478909 reaction equation
[CH2:1]([N:3]1[C:11]2[CH:10]=[C:9]([NH2:12])[N:8]=[CH:7][C:6]=2[CH:5]=[CH:4]1)[CH3:2].[CH2:13]=[C:14]([C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=1)[CH3:15].[H-].[Na+]>N1C=CC=CC=1>[CH2:1]([N:3]1[C:11]2[CH:10]=[C:9]([NH:12][C:20](=[O:21])[C:19]3[CH:23]=[CH:24][C:16]([C:14]([CH3:15])=[CH2:13])=[CH:17][CH:18]=3)[N:8]=[CH:7][C:6]=2[CH:5]=[CH:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67354123HCID 67354123, compound2×HCID 86674846HCID 86674846, compound2×

Product 1

HCID 67354739N-(1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(prop-1-en-2-yl)benzamideYield 81%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

In a 50 mL pear flask were added 1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-amine, TFA (1I, 5.2 g, 19 mmol) in pyridine (200 ml). At 0° C., 4-(prop-1-en-2-yl)benzoyl chloride (3.8 g, 21 mmol) was added. After 15 minutes, sodium hydride (0.53 g, 13 mmol) was added, and the reaction was stirred at room temperature for four hours. At 0° C., an additional 0.55 equivalent of 4-(prop-1-en-2-yl)benzoyl chloride was added and the reaction mixture was let stirred for another 15 hours at room temperature. The reaction was quenched by adding saturated NaHCO3 at 0° C. and stirred for 30 minutes. Volatiles were removed in vacuo, and the residue was extracted with ethyl acetate twice. Combined organic layers were dried over MgSO4, filtered and concentrated. The crude mixture was then purified by normal phase column chromatography (SiO2, eluting 20-50% EtOAc) to give the desired product N-(1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(prop-1-en-2-yl)benzamide (5A, 4.7 g, 15 mmol, 81% yield). 1H NMR (DMSO-d6) δ: 10.61 (s, 4 H), 8.64 (s, 4 H), 8.32 (s, 4 H), 8.04-8.10 (m, 9 H), 7.62-7.67 (m, 9 H), 7.47 (d, J=3.3 Hz, 4 H), 6.57 (dd, J=3.2, 0.9 Hz, 5 H), 5.58 (s, 4 H), 5.23 (t, J=1.4 Hz, 4 H), 4.21 (q, J=7.2 Hz, 9 H), 2.16 (d, J=0.5 Hz, 13 H), 1.39 (t, J=7.2 Hz, 3 H); m.p. 125-8° C.

Workup

  1. stirringthe reaction mixture was let stirred for another 15 hours at room temperature
  2. customThe reaction was quenched
  3. additionby adding saturated NaHCO3 at 0° C.
  4. stirringstirred for 30 minutes
  5. customVolatiles were removed in vacuo
  6. extractionthe residue was extracted with ethyl acetate twice
  7. dry with materialCombined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude mixture was then purified by normal phase column chromatography (SiO2, eluting 20-50% EtOAc)

Sources & evidence

ORD record
ord-2592517de07b4129a6cb253c50ea4252
Source dataset
uspto-grants-2016_08
Patent number
US09403819B2

Reaction notes

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