Pyridine → HCID 67441500, compound

HRID 1400929Notes

Reaction equation

HRID 1400929 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17]([C:19]3[N:20]=[N:21][N:22]([CH2:24][CH2:25][N:26]4[CH2:30][CH2:29][CH2:28][CH2:27]4)[CH:23]=3)[S:18][C:11]=12)[NH2:5].[N:31]1[CH:36]=[CH:35][CH:34]=C[CH:32]=1.ClC(OC1C=CC=CC=1)=[O:39].C1(N)CC1>CN(C=O)C.CCOC(C)=O.CCOCC>[CH:36]1([NH:31][C:32]([NH:5][C:4]2[CH:6]=[CH:7][C:8]([O:9][C:10]3[CH:15]=[CH:14][N:13]=[C:12]4[CH:16]=[C:17]([C:19]5[N:20]=[N:21][N:22]([CH2:24][CH2:25][N:26]6[CH2:27][CH2:28][CH2:29][CH2:30]6)[CH:23]=5)[S:18][C:11]=34)=[C:2]([F:1])[CH:3]=2)=[O:39])[CH2:34][CH2:35]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 58474870HCID 58474870, compound

Product 1

HCID 67441500HCID 67441500, compoundYield 42.6%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 361 (98 mg, 0.231 mmol) and pyridine (0.057 mL, 3 eq, 0.9 mmol) in DMF (5 mL) at 0° C. under nitrogen was added phenyl chloroformate (0.072 ml, 2.5 eq, 0.577 mmol) and the reaction mixture was stirred at 0° C. for 2 hrs. Cyclopropylamine (66 mg, 5 eq, 1.154 mmol) was added and the reaction mixture was heated at 55° C. for 5 hrs. The reaction mixture was then diluted with EtOAc, washed sequentially with sodium bicarbonate solution, saturated ammonium chloride solution and brine, then dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography (eluent EtOAc to 30% MeOH in EtOAc) to afford the title compound 362 (50 mg, 42% yield) as a while solid after additional trituration with Et2O. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.8 (s, 1H), 8.71 (s, 1H), 8.48 (d, J=5.48 Hz, 1H), 7.91 (s, 1H), 7.70 (m, 1H), 7.36 (m, 1H), 7.18 (d, J=8.99 Hz, 1H), 6.61 (d, J=5.48 hz, 1H), 6.55 (s, 1H), 4.55 (m, 2H), 2.93 (m, 2H), 2.50 (m, 1H), 1.67 (m, 4H), 0.65 (m, 2H), 0.41 (m, 2H). MS (m/z): 508.54.

Workup

  1. temperaturethe reaction mixture was heated at 55° C. for 5 hrs
  2. washwashed sequentially with sodium bicarbonate solution, saturated ammonium chloride solution and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (eluent EtOAc to 30% MeOH in EtOAc)

Sources & evidence

ORD record
ord-e34055da633c4104ad137f70e52c48e9
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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