Methanol → HCID 90750384, compound

HRID 644066Notes

Reaction equation

HRID 644066 reaction equation
C(O[C:4]([C:6]1[C:7]([C:16]2[C:24]3[C:19](=[C:20]([O:25][CH3:26])[CH:21]=[CH:22][CH:23]=3)[N:18]([CH2:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[CH:17]=2)=[N:8][S:9][C:10]=1[C:11]([O:13]CC)=O)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+].CO.[CH3:59][S:60](Cl)(=[O:62])=[O:61].C(N(CC)CC)C.[Cl:71]CCl>O1CCCC1.C(OCC)C>[Cl:71][CH2:4][C:6]1[C:7]([C:16]2[C:24]3[C:19](=[C:20]([O:25][CH3:26])[CH:21]=[CH:22][CH:23]=3)[N:18]([CH2:27][CH:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]3)[CH:17]=2)=[N:8][S:9][C:10]=1[CH2:11][O:13][S:60]([CH3:59])(=[O:62])=[O:61]

Participants

10

Reactant 7

HCID 887Methanol2×HCID 6344DichloromethaneHCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 62649Sodium sulfate decahydrateHCID 21226445Aluminium lithium hydrideHCID 68698973HCID 68698973, compound

Product 1

HCID 90750384HCID 90750384, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a cooled solution (ice/methanol bath) of 3-(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-isothiazole-4,5-dicarboxylic acid diethyl ester (400 mg, 0.85 mmol) in tetrahydrofuran (20 ml) was added lithium aluminium hydride (1M solution in THF; 1.91 ml, 1.91 mmol) and the reaction mixture stirred for 20 minutes. To the reaction mixture was added excess sodium sulfate decahydrate and the reaction stirred vigorously for 1.5 hours. The resulting mixture was filtered through a pad of dicalite, washing with diethyl ether. The filtrate was concentrated in vacuo and the resulting oil purified by flash column chromatography to afford 3-(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-4-hydroxymethyl-isothiazol-5-yl]-methanol (141 mg, 0.3 mmol). To a solution of 3-(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-4-hydroxymethyl-isothiazol-5-yl]-methanol (194 mg, 0.5 mmol) in dichloromethane (10 ml) was added methanesulfonyl chloride (0.182 ml, 1.16 mmol) followed by triethylamine (0.175 ml, 1.26 mmol) and the reaction mixture stirred for 45 minutes. A further portion of methanesulfonyl chloride (0.07 ml, 0.44 mmol) and triethylamine (0.15 ml, 1 mmol) was added and the reaction stirred for a further 2 hours. The reaction mixture was poured into a separating funnel, washed with 5% aqueous sodium carbonate solution, then brine, dried over magnesium sulfate and the solvent evaporated in vacuo. The resulting residue was purified by flash column chromatography using 33%-100% (v/v) dichloromethane in heptane and then diethyl ether to afford methanesulfonic acid {4-chloromethyl-3-[1-(cyclohexyl)methyl-7-methoxy-1H-indol-3-yl]-isothiazol-5-yl}methyl ester (113 mg, 0.23 mmol).

Workup

  1. stirringthe reaction stirred vigorously for 1.5 hours
  2. filtrationThe resulting mixture was filtered through a pad of dicalite
  3. washwashing with diethyl ether
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe resulting oil purified by flash column chromatography
  6. stirringthe reaction mixture stirred for 45 minutes
  7. stirringthe reaction stirred for a further 2 hours
  8. additionThe reaction mixture was poured into a separating funnel
  9. washwashed with 5% aqueous sodium carbonate solution
  10. dry with materialbrine, dried over magnesium sulfate
  11. customthe solvent evaporated in vacuo
  12. customThe resulting residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-f57df0dec89e4285ad1d7a12d8460896
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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