Cyclopropylamine → HCID 67441767, compound

HRID 1400837Notes

Reaction equation

HRID 1400837 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:21]=[CH:20][C:19]([C:22]([N:24]5[CH2:28][CH2:27][CH2:26][CH2:25]5)=[O:23])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:31])[CH:3]=1.ClC(Cl)(O[C:36](=[O:42])OC(Cl)(Cl)Cl)Cl.[CH:44]1([NH2:47])[CH2:46][CH2:45]1>C(Cl)Cl>[CH:44]1([NH:47][C:36]([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]=[CH:18][C:19]([C:22]([N:24]6[CH2:28][CH2:27][CH2:26][CH2:25]6)=[O:23])=[CH:20][CH:21]=5)[S:15][C:8]=34)=[C:4]([F:31])[CH:3]=2)=[O:42])[CH2:46][CH2:45]1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 94429TriphosgeneHCID 58474497HCID 58474497, compound

Product 1

HCID 67441767HCID 67441767, compoundYield 22.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 126 (150 mg, 0.346 mmol) in DCM (7 mL) was added TEA (105 mg, 1.038 mmol) and triphosgene (103 mg, 0.346 mmol) and the reaction mixture was stirred for 30 minutes. Cyclopropylamine (39.5 mg, 0.692 mmol) was added and the mixture was stirred at RT overnight. The mixture was concentrated and re-dissolved in EtOAc then washed with saturated NH4Cl solution. The organic phase was dried over anhydrous Na2SO4, filtered and concentrated. Purification by column chromatography (10% MeOH in EtOAc) afforded title compound 129 (40 mg, 22% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.71 (s, 1H), 8.51 (m, 1H), 8.13 (s, 1H), 7.93 (d, J=7.82 Hz, 2H), 7.73 (m, 1H), 7.63 (d, J=7.82 Hz, 2H), 7.37 (t, J=8.61 Hz, 1H), 7.18 (m, 1H), 6.61 (m, 1H), 6.56 (s, 1H), 3.47-3.42 (m, 4H), 1.86-1.81 (m, 4H), 2.53 (m, 1H), 0.64 (m, 2H), 0.411 (m, 2H). MS (m/z)=517.533 (M+H)

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. concentrationThe mixture was concentrated
  3. dissolutionre-dissolved in EtOAc
  4. washthen washed with saturated NH4Cl solution
  5. dry with materialThe organic phase was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography (10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-ca2340e78a09452695a1173c86dca7cd
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

Loading…