Cyclopropylamine → HCID 118284055, compound

HRID 526013Notes

Reaction equation

HRID 526013 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.C[Al](C)C.[CH2:9]([N:11]1[C:19]2[C:14](=[N:15][C:16]([C:20](OC)=[O:21])=[CH:17][CH:18]=2)[CH:13]=[C:12]1[C:24](=[O:42])[NH:25][CH:26]([C:31]1[CH:36]=[CH:35][C:34]([F:37])=[C:33]([C:38]([F:41])([F:40])[F:39])[CH:32]=1)[C:27]([F:30])([F:29])[F:28])[CH3:10]>ClCCl>[CH:1]1([NH:4][C:20]([C:16]2[N:15]=[C:14]3[CH:13]=[C:12]([C:24]([NH:25][CH:26]([C:31]4[CH:36]=[CH:35][C:34]([F:37])=[C:33]([C:38]([F:39])([F:40])[F:41])[CH:32]=4)[C:27]([F:29])([F:28])[F:30])=[O:42])[N:11]([CH2:9][CH3:10])[C:19]3=[CH:18][CH:17]=2)=[O:21])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 16682925TrimethylaluminumHCID 90039460HCID 90039460, compound

Product 1

HCID 118284055HCID 118284055, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Under an atmosphere of argon protective gas, cyclopropylamine (58.1 mg, 1.02 mmol) was added to one ml of dichloromethane, and trimethylaluminium (73.4 mg, 1.02 mmol) was added dropwise using a syringe. The mixture was stirred for another 30 minutes, and methyl 1-ethyl-2-({2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-pyrrolo[3,2-b]pyridine-5-carboxylate, dissolved in one ml of dichloromethane, was then added dropwise. The reaction mixture was then heated under reflux for six hours and subsequently cooled and hydrolysed, and the residue was, after removal of the volatile components under reduced pressure, chromatographed on silica gel cyclohexane/ethyl acetate (ethyl acetate 0% to 60%). This gave 20 mg (35% of theory) of the target product. HPLC-MS: log P=3.78; mass (m/z): 517.1 (M+H)+; 1HNMR (D6-DMSO): δ 0.54-0.76 (m, 4H), 1.22-1.30 (t, 3H), 2.88-2.94 (m, 1H), 4.48-4.59 (q, 2H), 6.32-6.42 (m, 1H), 7.42 (s, 1H), 7.65-7.71 (t, 1H), 7.98-8.02 (d, 1H), 8.14-8.20 (m, 1H), 8.20-8.24 (d, 1H), 8.26-8.32 (m, 1H), 8.56-8.62 (d, 1H), 9.91 (s, 1H).

Workup

  1. additionwas added dropwise
  2. additionwas then added dropwise
  3. temperatureThe reaction mixture was then heated
  4. temperatureunder reflux for six hours
  5. temperaturesubsequently cooled
  6. customafter removal of the volatile components under reduced pressure
  7. customchromatographed on silica gel cyclohexane/ethyl acetate (ethyl acetate 0% to 60%)

Sources & evidence

ORD record
ord-2084ad3e54404ac3ad27b4d5fb1f73f5
Source dataset
uspto-grants-2016_05
Patent number
US09345247B2

Reaction notes

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