Cyclopropylamine → HCID 67443336, compound

HRID 1400841Notes

Reaction equation

HRID 1400841 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[N:17]([CH3:28])[C:18]([CH2:21][N:22]5[CH2:26][CH2:25][CH2:24][C:23]5=[O:27])=[CH:19][N:20]=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>C1COCC1>[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[N:17]([CH3:28])[C:18]([CH2:21][N:22]6[CH2:26][CH2:25][CH2:24][C:23]6=[O:27])=[CH:19][N:20]=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 58474845HCID 58474845, compound

Product 1

HCID 67443336HCID 67443336, compoundYield 51.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 136 (77 mg, 0.176 mmol) in THF (10 mL) was added TEA (0.074 mL, 0.528 mmol) and triphosgene (52.2 mg, 1.451 mmol) in THF (5 mL) and the mixture was stirred at RT for an hour. Cyclopropylamine (10.5 mg, 0.176 mmol) was added and the reaction mixture was stirred at RT overnight. The reaction mixture was then concentrated and partitioned between with DCM and saturated NaHCO3 solution. The organic phase was collected, dried over anhydrous Na2SO4, filtered and concentrated. Purification of the residue by column chromatography (10% MeOH in EtOAc) afforded title compound 137 (47 mg, 51% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.69 (s, 1H), 8.50 (d, J=5.48 Hz, 1H), 7.89 (s, 1H), 7.70 (m, 1H), 7.35 (t, J=8.99 Hz, 1H), 7.17 (m, 1H), 7.05 (s, 1H), 6.65 (d, J=5.48 Hz, 1H), 6.55 (m, 1H), 4.46 (s, 2H), 3.82 (s, 3H), 3.22 (t, J=6.84 Hz, 2H), 2.52 (m, 1H), 2.27 (t, J=7.82 Hz, 2H), 1.90 (m, 2H), 0.63 (m, 2H), 0.40 (m, 2H). MS (m/z)=521.638 (M+H)

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. concentrationThe reaction mixture was then concentrated
  3. custompartitioned between with DCM and saturated NaHCO3 solution
  4. customThe organic phase was collected
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by column chromatography (10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-a6dcb10f19704931bef9affbf64bd55d
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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