Ethylamine → HCID 131728075, compound

HRID 644067Notes

Reaction equation

HRID 644067 reaction equation
[Cl:1][CH2:2][C:3]1[C:4]([C:14]2[C:22]3[C:17](=[C:18]([O:23][CH3:24])[CH:19]=[CH:20][CH:21]=3)[N:16]([CH2:25][CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[CH:15]=2)=[N:5][S:6][C:7]=1[CH2:8]OS(C)(=O)=O.[CH2:32]([NH2:34])[CH3:33].C(N(CC)CC)C>O1CCCC1.ClCCl>[ClH:1].[CH:26]1([CH2:25][N:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][C:18]=3[O:23][CH3:24])[C:14]([C:4]3[C:3]4[CH2:2][N:34]([CH2:32][CH3:33])[CH2:8][C:7]=4[S:6][N:5]=3)=[CH:15]2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

6

Reactant 3

HCID 6341EthylamineHCID 8471TriethylamineHCID 90750384HCID 90750384, compound

Product 1

HCID 131728075HCID 131728075, compoundYield 47.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methanesulfonic acid {4-chloromethyl-3-[1-(cyclohexyl)methyl-7-methoxy-1H-indol-3-yl]-isothiazol-5-yl}methyl ester (90 mg, 0.19 mmol) in tetrahydrofuran (1 ml) was added ethylamine (0.186 ml, 0.37 mmol) and triethylamine (0.05 ml, 0.37 mmol) and the reaction mixture subjected to microwave irradiation at 150° C. for 15 minutes. The reaction mixture was poured into a separating funnel, diluted with dichloromethane (30 ml) and washed with 5% aqueous sodium carbonate solution (2×10 ml), brine (10 ml), dried over magnesium sulfate and the solvent removed in vacuo. The reaction was repeated on a 0.166 mmol scale to give the same intermediate. The crude products were combined and purified by flash column chromatography using ethyl acetate to give the title compound (36 mg, 0.09 mmol) as the free base. The free base was dissolved in dichloromethane and hydrogen chloride (2M solution in diethyl ether; 1 ml, 2 mmol) was added. The mixture was concentrated in vacuo to afford the title compound as a 1:1 hydrochloride salt. 1H NMR (400 MHz, CD3OD): 0.97-1.15 (2H, m), 1.15-1.27 (3H, m), 1.47 (3H, t, J 7), 1.52-1.61 (2H, m), 1.62-1.77 (3H, m), 1.81-1.95 (1H, m), 3.63 (2H, q, J 7), 3.95 (3H, s), 4.28 (2H, d, J 7), 4.62-4.75 (2H, m), 4.95-5.12 (2H, m), 6.77 (1H, d, J 8), 7.09 (1H, t, J 8), 7.43 (1H, s), 8.01 (1H, d, J 8); EsIMS: m/z 396.0 [M+H]+, 353.4, 351.3, 320.3.

Workup

  1. customirradiation at 150° C. for 15 minutes
  2. additionThe reaction mixture was poured into a separating funnel
  3. washwashed with 5% aqueous sodium carbonate solution (2×10 ml), brine (10 ml)
  4. dry with materialdried over magnesium sulfate
  5. customthe solvent removed in vacuo
  6. customto give the same intermediate
  7. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-c602a0bca5e941a6849a9abec1120720
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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