Dimethylformamide → HCID 57700916, compound

HRID 468456Notes

Reaction equation

HRID 468456 reaction equation
O=P(Cl)(Cl)Cl.[O:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3([C:18]([NH:20][C:21]4[CH:22]=[C:23]5[C:27](=[CH:28][CH:29]=4)[NH:26][C:25]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:24]5)=[O:19])[CH2:17][CH2:16]3)=[CH:14][C:9]=2[O:8][CH2:7]1.CN([CH:37]=[O:38])C>>[O:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3([C:18]([NH:20][C:21]4[CH:22]=[C:23]5[C:27](=[CH:28][CH:29]=4)[NH:26][C:25]([C:30]([CH3:33])([CH3:32])[CH3:31])=[C:24]5[CH:37]=[O:38])=[O:19])[CH2:17][CH2:16]3)=[CH:14][C:9]=2[O:8][CH2:7]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 247629031-(Benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-1H-indol-5-yl)cyclopropanecarboxamide

Product 1

HCID 57700916HCID 57700916, compoundYield 61%

Conditions

Temperature
0 °C

Procedure

POCl3 (12 g, 80 mmol) was added dropwise to DMF (40 mL) held at −20° C. After the addition was complete, the reaction mixture was allowed to warm to 0° C. and was stirred for 1 h. 1-(Benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-1H-indol-5-yl)cyclopropanecarbox amide (3.0 g, 8.0 mmol) was added and the mixture was warmed to 25° C. After stirring for 30 minutes the reaction mixture was poured over ice and stirred for 2 h. The mixture was then heated at 100° C. for 30 min. The mixture was cooled and the solid precipitate was collected and washed with water. The solid was then dissolved in 200 mL dichloromethane and washed with 200 mL of a saturated aq. NaHCO3. The organics were dried over Na2SO4 and evaporated to yield 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-3-formyl-1H-indol-5-yl)cyclopropane-carboxamide (2.0 g, 61%). ESI-MS m/z calc. 404.5, found 405.5 (M+1)+; retention time 3.30 minutes. 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 10.39 (5, 1H), 8.72 (s, 1H), 8.21 (s, 1H), 7.35-7.31 (m, 2H), 7.04-7.03 (m, 1H), 6.97-6.90 (m, 2H), 6.03 (s, 2H), 1.53 (s, 9H), 1.42-1.39 (m, 2H), 1.05-1.03 (m, 2H).

Workup

  1. customheld at −20° C
  2. additionAfter the addition
  3. temperaturethe mixture was warmed to 25° C
  4. stirringAfter stirring for 30 minutes the reaction mixture
  5. additionwas poured over ice
  6. stirringstirred for 2 h
  7. temperatureThe mixture was then heated at 100° C. for 30 min
  8. temperatureThe mixture was cooled
  9. customthe solid precipitate was collected
  10. washwashed with water
  11. dissolutionThe solid was then dissolved in 200 mL dichloromethane
  12. washwashed with 200 mL of a saturated aq. NaHCO3
  13. dry with materialThe organics were dried over Na2SO4
  14. customevaporated

Sources & evidence

ORD record
ord-20c82e8088f5468dae9d090998b06369
Source dataset
uspto-grants-2014_01
Patent number
US08623905B2

Reaction notes

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