Cyclopropylamine → HCID 67442248, compound

HRID 1400804Notes

Reaction equation

HRID 1400804 reaction equation
[NH2:1][C:2]1[CH:36]=[CH:35][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]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:37])[C:3]=1[F:38].CC[N:41]([CH:45]([CH3:47])[CH3:46])[CH:42](C)C.ClC(Cl)([O:51]C(=O)OC(Cl)(Cl)Cl)Cl.C1(N)CC1>C1COCC1>[CH:45]1([NH:41][C:42](=[O:51])[NH:1][C:2]2[CH:36]=[CH:35][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]4[CH:13]=[C:14]([C:16]5[N:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:18][CH:17]=5)[S:15][C:8]=34)=[C:4]([F:37])[C:3]=2[F:38])[CH2:46][CH2:47]1

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 67442310HCID 67442310, compound

Product 1

HCID 67442248HCID 67442248, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-25 °C

Procedure

To a stirred solution of aniline 23 (500 mg, 0.92 mmol) and DIPEA (0.8 mL, 4.61 mmol) in THF (18 mL) at −25° C. under nitrogen was added dropwise a solution of triphosgene (273 mg, 0.920 mmol) in THF (2 mL). The reaction mixture was stirred at −25° C. and cyclopropylamine (0.32 mL, 4.61 mmol) was slowly added. The reaction mixture was allowed to warm to RT over 1.5 h and stirred at RT overnight. The reaction mixture was then partitioned between AcOEt and water. The organic layer was successively washed with a saturated aqueous solution of ammonium chloride, 1N NaOH and brine, dried over anhydrous magnesium sulfate, filtered and concentrated to afford the title compound 24 as an off-white solid. The crude material was used in the next step without any further purification. MS (m/z): 626.6 (M+H).

Workup

  1. temperatureto warm to RT over 1.5 h
  2. stirringstirred at RT overnight
  3. customThe reaction mixture was then partitioned between AcOEt and water
  4. washThe organic layer was successively washed with a saturated aqueous solution of ammonium chloride, 1N NaOH and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c000547d4f084262b51bf5af04b2f6f8
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

Loading…