Hydrochloric Acid → 1-(Cyclohexyl)methyl-3-{2-[(diethylamino)methyl]-[1,3]-oxazol-5-yl}-7-methoxy-1H-indole, hydrochloride salt

HRID 644065Notes

Reaction equation

HRID 644065 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][CH2:6][C:7]([C:9]1[C:17]2[C:12](=[C:13]([O:18][CH3:19])[CH:14]=[CH:15][CH:16]=2)[N:11]([CH2:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[CH:10]=1)=[O:8])=O.[CH2:27]([NH:29][CH2:30][CH3:31])[CH3:28].Cl>O1CCCC1.[OH-].COC(NS([N+](CC)(CC)CC)(=O)=O)=O.ClCCl>[ClH:1].[CH:21]1([CH2:20][N:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][C:13]=3[O:18][CH3:19])[C:9]([C:7]3[O:8][C:3]([CH2:2][N:29]([CH2:30][CH3:31])[CH2:27][CH3:28])=[N:5][CH:6]=3)=[CH:10]2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 8021DiethylamineHCID 687020002-chloro-N-[2-(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-2-oxoethyl]-acetamide

Product 1

HCID 1317280741-(Cyclohexyl)methyl-3-{2-[(diethylamino)methyl]-[1,3]-oxazol-5-yl}-7-methoxy-1H-indole, hydrochloride salt

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 11032497(Methoxycarbonylsulfamoyl)triethylammonium hydroxideSolvent

Procedure

To a solution of 2-chloro-N-[2-(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-2-oxoethyl]-acetamide (200 mg, 0.53 mmol) in tetrahydrofuran (2 ml) was added diethylamine (0.55 ml, 5.3 mmol) and the reaction mixture subjected to microwave irradiation at 150° C. for 15 minutes. The reaction mixture was poured into a separating funnel and dichloromethane (30 ml) added. The organics were washed sequentially with 5% aqueous sodium carbonate and brine. The organics were dried over magnesium sulfate, filtered and the solvent removed in vacuo to give a brown solid. The brown solid was dissolved in tetrahydrofuran (2 ml) and (methoxycarbonylsulfamoyl)triethylammonium hydroxide, inner salt (505 mg, 2.12 mmol) added. The resulting reaction mixture was subjected to microwave irradiation at 150° C. for 15 minutes and quenched with methanol (20 ml). The solvent was removed in vacuo and the residue purified by flash chromatography using 50% (v/v) ethyl acetate in heptane, followed by semi-prep. HPLC [Method (ii)] to afford a white solid. The solid was dissolved in dichloromethane (˜5 ml) and hydrogen chloride (1M solution in diethyl ether; 1 ml) added. The mixture was concentrated in vacuo to afford the title compound as a 1:1 hydrochloride salt (77 mg, 0.2 mmol). 1H NMR (400 MHz, CD3OD) δH 0.97-1.12 (2H, m), 1.15-1.25 (3H, m), 1.44 (6H, t, J 6.9), 1.52-1.62 (2H, m), 1.62-1.77 (3H, m), 1.77-1.9 (1H, m), 3.36 (4H, q, J 6.7), 3.95 (3H, s), 4.26 (2H, d, J 7), 4.64 (2H, s), 6.77 (1H, d, J 8), 7.11 (1H, t, J 8), 7.38 (1H, s), 7.41 (1H, d, J 8), 7.56 (1H, s); EsIMS: m/z 396.1 [M+H]+, 323.4, 268.4.

Workup

  1. customirradiation at 150° C. for 15 minutes
  2. additionThe reaction mixture was poured into a separating funnel
  3. washThe organics were washed sequentially with 5% aqueous sodium carbonate and brine
  4. dry with materialThe organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customto give a brown solid
  8. customThe resulting reaction mixture
  9. customirradiation at 150° C. for 15 minutes
  10. customquenched with methanol (20 ml)
  11. customThe solvent was removed in vacuo
  12. customthe residue purified by flash chromatography
  13. customHPLC [Method (ii)] to afford a white solid
  14. concentrationThe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-a4bbf6f36bb540d683421ebcad32d0ed
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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