Cyclopropylamine → HCID 67443029, compound

HRID 1400869Notes

Reaction equation

HRID 1400869 reaction equation
[NH2:1][C:2]1[CH:34]=[CH:33][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]([CH3:32])[C:18]([C:21]([NH:23][CH2:24][CH2:25][N:26]5[CH2:31][CH2:30][O:29][CH2:28][CH2:27]5)=[O:22])=[CH:19][N:20]=4)[S:15][C:8]=23)=[C:4]([F:35])[CH:3]=1.CC[N:38]([CH:42]([CH3:44])[CH3:43])[CH:39](C)C.ClC(Cl)([O:48]C(=O)OC(Cl)(Cl)Cl)Cl.C1(N)CC1>C1COCC1>[CH:42]1([NH:38][C:39](=[O:48])[NH:1][C:2]2[CH:34]=[CH:33][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]([CH3:32])[C:18]([C:21]([NH:23][CH2:24][CH2:25][N:26]6[CH2:31][CH2:30][O:29][CH2:28][CH2:27]6)=[O:22])=[CH:19][N:20]=5)[S:15][C:8]=34)=[C:4]([F:35])[CH:3]=2)[CH2:43][CH2:44]1

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 58474588HCID 58474588, compound

Product 1

HCID 67443029HCID 67443029, compoundYield 39.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of aniline 216 (130 mg, 0.262 mmol) in THF (10 mL) at 0° C. was added DIPEA (0.137 mL, 0.785 mmol) and triphosgene (38.8 mg, 0.131 mmol). The reaction mixture was stirred at 0° C. for 1 hr before cyclopropylamine (0.054 mL, 0.785 mmol) was added and the mixture was stirred for 10 min at 0° C. The reaction mixture was slowly warmed to room temperature and stirred over weekend then partitioned between NaHCO3 saturated solution and EtOAc. The organic layer (suspension) was concentrated, the residue was dry-loaded onto a column (Biotage, MeOH/DCM, 0-25%, SNAP 10 g cartridge), purified twice then triturated with ether and acetone to give title compound 217 (30.4 mg, 0.052 mmol, 20% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.75 (s, 1H), 8.59 (d, 1H, J=5.5 Hz), 8.48 (m, 1H), 8.07 (s, 1H), 7.78-7.74 (m, 1H), 7.71 (s, 1H), 7.42 (t, 1H, J=9.0 Hz), 7.25-7.22 (m, 1H), 6.74 (d, 1H, J=5.5 Hz), 6.61-6.60 (m, 1H), 4.22 (s, 3H), 3.62 (t, 4H, J=4.5 Hz), inside 3.38-3.33 (m, 2H), 2.60-2.57 (m, 1H), 2.52-2.46 (m, 6H), 0.71-0.67 (m, 2H), 0.48-0.46 (m, 2H). MS: 580.6 (MH)+

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was slowly warmed to room temperature
  3. stirringstirred over weekend
  4. customthen partitioned between NaHCO3 saturated solution and EtOAc
  5. concentrationThe organic layer (suspension) was concentrated
  6. custompurified twice
  7. customthen triturated with ether and acetone

Sources & evidence

ORD record
ord-0282bf4c7d234701ac750be383feec2e
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

Loading…