Ethanolamine → 2-({[5-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3,4-thiadiazol-2-yl]methyl}amino)ethanol

HRID 1882109Notes

Reaction equation

HRID 1882109 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[S:30][C:29]([CH:31]=O)=[N:28][N:27]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[NH2:33][CH2:34][CH2:35][OH:36].[BH4-].[Na+].C(=O)([O-])O.[Na+]>CO>[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[S:30][C:29]([CH2:31][NH:33][CH2:34][CH2:35][OH:36])=[N:28][N:27]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)(=[O:5])=[O:6])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 700EthanolamineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 1361666495-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3,4-thiadiazole-2-carbaldehyde

Product 1

HCID 1361666512-({[5-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3,4-thiadiazol-2-yl]methyl}amino)ethanolYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3,4-thiadiazole-2-carbaldehyde (300 mg) in methanol (10 mL) was added 2-aminoethanol (250 μL) at room temperature, and the mixture was stirred at 80° C. for 1 hr. The reaction mixture was cooled to room temperature, sodium tetrahydroborate (72 mg) was added to the reaction mixture, and the mixture was stirred at room temperature for 30 min. Saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to basic silica gel column chromatography to give a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). The pale-yellow amorphous solid was subjected to silica gel column chromatography, and the title compound (188 mg, yield 57%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-methanol (8:2, volume ratio). MS: 517 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customto give a pale-yellow amorphous solid from a fraction
  8. washeluted with ethyl acetate-methanol (9:1, volume ratio)

Sources & evidence

ORD record
ord-132802caa3cc40448178a30084937d77
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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