Pyridine → HCID 67440984, compound

HRID 1400855Notes

Reaction equation

HRID 1400855 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:17]=[N:18][N:19]([CH2:21][CH2:22][N:23]5[CH2:27][CH2:26][CH2:25][C:24]5=[O:28])[CH:20]=4)[S:15][C:8]=23)=[C:4]([F:31])[CH:3]=1.[N:32]1[CH:37]=[CH:36][CH:35]=C[CH:33]=1.ClC(OC1C=CC=CC=1)=[O:40].C1(N)CC1>CN(C=O)C>[CH:37]1([NH:32][C:33]([NH:1][C:2]2[CH:30]=[CH:29][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]4[CH:13]=[C:14]([C:16]5[CH:17]=[N:18][N:19]([CH2:21][CH2:22][N:23]6[CH2:27][CH2:26][CH2:25][C:24]6=[O:28])[CH:20]=5)[S:15][C:8]=34)=[C:4]([F:31])[CH:3]=2)=[O:40])[CH2:35][CH2:36]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 58474785HCID 58474785, compound

Product 1

HCID 67440984HCID 67440984, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 165 (400 mg, 0.914 mmol) and pyridine (0.222 mL, 2.74 mmol) in DMF (10 mL) at 0° C. under nitrogen was added phenyl chloroformate (0.287 mg, 2.286 mmol) and the reaction mixture was stirred at 0° C. for 2 hrs. Cyclopropylamine (0.322 mL, 4.57 mmol) was added and the reaction mixture was heated at 55° C. for 5 hrs. The reaction mixture was partitioned between EtOAc and saturated sodium bicarbonate solution, then washed with saturated ammonium chloride solution and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (eluent EtOAc to 20% MeOH in EtOAc) to afford title compound 166 (250 mg, 53% yield) as a white solid. 1H NMR (400 MHz. DMSO-d6) δ (ppm): 8.69 (s, 1H), 8.44 (d, J=5.48 Hz, 1H), 8.35 (s, 1H), 8.035 (s, 1H), 7.74 (m, 1H), 7.70 (s, 1H), 7.35 (t, J=8.99 Hz, 1H), 7.19 (d, J=8.99 Hz, 1H), 6.55 (m, 2H), 4.28 (t, J=5.87 Hz, 2H), 3.59 (t, J=5.86 Hz, 2H), 3.17 (t, J=6.84 Hz, 2H), 2.55 (m, 1H), 2.15 (t, J=7.83 Hz, 2H), 1.86 (m, 2H), 0.64 (m, 2H), 0.42 (m, 2H). MS (m/z)=521.38 (M+H)

Workup

  1. temperaturethe reaction mixture was heated at 55° C. for 5 hrs
  2. customThe reaction mixture was partitioned between EtOAc and saturated sodium bicarbonate solution
  3. washwashed with saturated ammonium chloride solution and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (eluent EtOAc to 20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-3474ef04b8a34723b1983f68f9749da8
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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