Cyclopropylamine → HCID 67443346, compound

HRID 1400844Notes

Reaction equation

HRID 1400844 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[N:21]=[CH:20][C:19]([CH2:22][N:23]5[C:27](=[O:28])[CH2:26][CH2:25][C:24]5=[O:29])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:32])[CH:3]=1.ClC(Cl)(O[C:37](=[O:43])OC(Cl)(Cl)Cl)Cl.[CH:45]1([NH2:48])[CH2:47][CH2:46]1>C1COCC1.CCOC(C)=O>[CH:45]1([NH:48][C:37]([NH:1][C:2]2[CH:31]=[CH:30][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]([CH2:22][N:23]6[C:24](=[O:29])[CH2:25][CH2:26][C:27]6=[O:28])=[CH:20][N:21]=5)[S:15][C:8]=34)=[C:4]([F:32])[CH:3]=2)=[O:43])[CH2:47][CH2:46]1

Participants

6

Reactant 3

HCID 69828CyclopropylamineHCID 94429TriphosgeneHCID 58474350HCID 58474350, compound

Product 1

HCID 67443346HCID 67443346, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 139 (101 mg, 0.225 mmol) in THF (6 mL) at −35° C. was added TEA (0.094 mL, 1.126 mmol) and triphosgene (80 mg, 0.270 mmol) in THF (1 mL) and the mixture was warmed to −10° C. over an hr. Cyclopropylamine (64.3 mg, 1.126 mmol) was added and the reaction mixture was stirred at RT for 1.5 hrs. The reaction mixture was diluted with EtOAc then washed with saturated NH4Cl solution. The organic phase was collected, dried over anhydrous Na2SO4, filtered and concentrated. Purification by column chromatography (10% MeOH in EtOAc) afforded title compound 140 (20 mg, 17% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.69 (s, 1H), 8.53 (s, 1H), 8.50 (d, J=5.48 Hz, 1H), 8.32 (s, 1H), 8.22 (d, J=8.021, 1H), 7.81 (m, 1H), 7.70 (m, 1H), 7.36 (t, J=9.19 Hz, 1H), 7.18 (m, 1H), 6.62 (d, J=4.89 Hz, 1H), 6.55 (s, 1H), 4.62 (s, 2H), 2.68 (s, 4H), 2.53 (m, 1H), 0.63 (m, 2H), 0.41 (m, 2H). M (m/z)=532.543 (M+H)

Workup

  1. washthen washed with saturated NH4Cl solution
  2. customThe organic phase was collected
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by column chromatography (10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-a21b564c8e9a4d1ba978462c27bce448
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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