Cyclopropylamine → HCID 89783610, compound

HRID 1056189Notes

Reaction equation

HRID 1056189 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:12]2[NH:13][C:14]([C:22]3[CH:31]=[CH:30][CH:29]=[C:28]4[C:23]=3[N:24]=[C:25](F)[C:26]([CH3:32])=[N:27]4)=[CH:15][C:16]=2[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:34]1([NH2:37])[CH2:36][CH2:35]1.CCN(C(C)C)C(C)C>CS(C)=O.CCOC(C)=O>[C:1]([O:5][C:6]([NH:8][C:9]1([C:12]2[NH:13][C:14]([C:22]3[CH:31]=[CH:30][CH:29]=[C:28]4[C:23]=3[N:24]=[C:25]([NH:37][CH:34]3[CH2:36][CH2:35]3)[C:26]([CH3:32])=[N:27]4)=[CH:15][C:16]=2[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 89783515HCID 89783515, compound

Product 1

HCID 89783610HCID 89783610, compoundYield 56.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (325b) (218 mg, 0.480 mmol), cyclopropanamine (82 mg, 1.44 mmol) and DIEA (0.17 mL, 0.96 mmol) in 3 mL of DMSO was heated in an oil bath at 80° C. for 5 h. It was diluted with 50 mL of EtOAc, washed with 5 mL of water. The organic solution was concentrated and the residue was stirred in 5 mL of ether. The insoluble yellow solid was filtered, rinsed with 2×2 mL of ether to give 133 mg of ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate, as a yellow crystalline solid. The filtrate was concentrated and the residue was purified on a silica gel column (25-70% EtOAc in Hexanes) to give 67 mg ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.31 (1H, br.), 8.05 (1H, m), 7.61 (1H, dd, J=8.0, 1.2 Hz), 7.42 (1H, d, J=3.5 Hz), 7.35 (1H, t, J=7.8 Hz), 7.26 (1H, br.), 7.02 (2H, br.), 4.28 (2H, q, J=7.0 Hz), 2.56 (3H, s), 1.35 (4H, m), 1.32 (9H, s), 1.03-1.19 (5H, m), 0.63-0.78 (2H, m). m/z (ESI, +ve) 492.2 (M+H)+.

Workup

  1. washwashed with 5 mL of water
  2. concentrationThe organic solution was concentrated
  3. filtrationThe insoluble yellow solid was filtered
  4. washrinsed with 2×2 mL of ether

Sources & evidence

ORD record
ord-685036b709bd45a091bbd762e8214ea2
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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