Pyridine → HCID 67441039, compound

HRID 1400915Notes

Reaction equation

HRID 1400915 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[CH:8][C:9]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:28]=[CH:27][C:25]([NH2:26])=[C:24]([F:29])[C:23]=3[F:30])[CH:13]=2)=[N:10][CH:11]=1.[N:31]1[CH:36]=C[CH:34]=[CH:33][CH:32]=1.ClC(OC1C=CC=CC=1)=[O:39].C1(N)CC1>CN(C=O)C.O>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[CH:8][C:9]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:28]=[CH:27][C:25]([NH:26][C:36]([NH:31][CH:32]4[CH2:34][CH2:33]4)=[O:39])=[C:24]([F:29])[C:23]=3[F:30])[CH:13]=2)=[N:10][CH:11]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 58474318HCID 58474318, compound

Product 1

HCID 67441039HCID 67441039, compoundYield 86.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 302 (1.7 g, 3.98 mmol) in DMF (7 mL) was added pyridine (0.55 mL, 6.77 mmol) at RT and the resultant reaction mixture was stirred for 10 min under Ar atmosphere. Phenyl chloroformate (0.75 mL, 5.97 mmol) was added at 0° C. and the mixture was stirred at RT for an additional 40 min. Cyclopropylamine (1.1 mL, 15.9 mmol) was added to the mixture, and the reaction mixture was warmed to 50° C. and stirred for 2 hours. The mixture was then cooled, poured into water (150 mL) and stirred for 30 min. The precipitate was collected by filtration, washed with water and dried overnight. The crude product was triturated with EtOAc for 1 h and collected by filtration to afford title compound 303 (1.75 g, 86% yield) as a pale violet solid. 1H NMR (300 MHz, DMSO-d6) δ (ppm): 8.71 (d, J=2.1 Hz, 1H), 8.55 (d, J=5.4 Hz, 1H), 8.46 (s, 1H), 8.42 (s, 1H), 8.33 (d, J=8.1 Hz, 1H), 8.10-7.95 (m, 1H), 7.99 (dd, J=8.1, 2.1 Hz, 1H), 7.40-7.22 (m, 1H), 6.87 (br, 1H), 6.78 (d, J=5.1 Hz, 1H), 5.90 (s, 1H), 4.16-3.96 (m, 4H), 2.64-2.50 (m, 1H), 0.75-0.60 (m, 2H), 0.50-0.35 (m, 2H)

Workup

  1. customthe resultant reaction mixture
  2. stirringthe mixture was stirred at RT for an additional 40 min
  3. stirringstirred for 2 hours
  4. temperatureThe mixture was then cooled
  5. stirringstirred for 30 min
  6. filtrationThe precipitate was collected by filtration
  7. washwashed with water
  8. customdried overnight
  9. customThe crude product was triturated with EtOAc for 1 h
  10. filtrationcollected by filtration

Sources & evidence

ORD record
ord-45b5fca78c26434aab10ed78bc8ec5fd
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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