1,2,3,4-Tetrahydroisoquinoline → (2R)-1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-[3-(1-methyl-1H-thieno[3,2-c]pyrazol-3-yl)-phenoxy]-propan-2-ol

HRID 1246568Notes

Reaction equation

HRID 1246568 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.[CH3:11][N:12]1[C:16]2[CH:17]=[CH:18][S:19][C:15]=2[C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH2:27][C@H:28]3[CH2:30][O:29]3)[CH:21]=2)=[N:13]1>C(O)C>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:30][C@@H:28]([OH:29])[CH2:27][O:26][C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([C:14]2[C:15]3[S:19][CH:18]=[CH:17][C:16]=3[N:12]([CH3:11])[N:13]=2)[CH:21]=1

Participants

4

Reactant 2

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 58720310(R)-1-methyl-3-(3-oxiranylmethoxy-phenyl)-1H-thieno[3,2-c]pyrazole

Product 1

HCID 58720296(2R)-1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-[3-(1-methyl-1H-thieno[3,2-c]pyrazol-3-yl)-phenoxy]-propan-2-ol

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

Add a solution of 1,2,3,4-tetrahydroisoquinoline (Aldrich Chemical Company) in absolute ethanol (0.0465 g, 0.200 M solution, 1.745 mL, 2.0 equiv.) to a reaction tube. Add absolute ethanol (3 mL) to the reaction tube and then add a solution of (R)-1-methyl-3-(3-oxiranylmethoxy-phenyl)-1H-thieno[3,2-c]pyrazole and absolute ethanol (example 8, 0.050 g, 0.200 M solution, 0.875 mL). Shake the reaction mixture under Argon at reflux temperature overnight in a Bohdan apparatus. Cool and concentrate to remove the solvent. Purify the residue by flash chromatography (5 g silica gel SepPak cartridge) eluting in step gradient fashion sequentially with 2% and 5% methanol in dichloromethane, and dichloromethane:methanol:ammonium hydroxide solution, 90:9:1. Combine and concentrate the desired fractions to give the title compound (0.0796 g), LC/MS (APCI, condition 3) m/e 420 (MH+), retention time 5.16 min.

Workup

  1. temperatureShake the reaction mixture under Argon at reflux temperature overnight in a Bohdan apparatus
  2. temperatureCool
  3. concentrationconcentrate
  4. customto remove the solvent
  5. customPurify the residue by flash chromatography (5 g silica gel SepPak cartridge)
  6. washeluting in step gradient fashion sequentially with 2% and 5% methanol in dichloromethane, and dichloromethane
  7. concentrationCombine and concentrate the desired fractions

Sources & evidence

ORD record
ord-4f8e8844b23a4d15bafcce1ea2a55b18
Source dataset
uspto-grants-2006_10
Patent number
US07125903B1

Reaction notes

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