Triethylamine → (R)-N-(5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)methanesulfonamide

HRID 42993Notes

Reaction equation

HRID 42993 reaction equation
[NH2:1][C@H:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:11][N:12]3[CH:16]=[C:15]([CH2:17][OH:18])[C:14]([C:19]([F:22])([F:21])[F:20])=[N:13]3)[CH:8]=2)[CH2:3]1.C(N(CC)CC)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>O1CCCC1.CS(C)=O>[OH:18][CH2:17][C:15]1[C:14]([C:19]([F:22])([F:21])[F:20])=[N:13][N:12]([CH2:11][C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[CH2:3][C@@H:2]([NH:1][S:31]([CH3:30])(=[O:33])=[O:32])[CH2:10]3)[CH:16]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 67026260(R)-(1-((2-amino-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)methanol

Product 1

HCID 67088075(R)-N-(5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)methanesulfonamideYield 29.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

(R)-(1-((2-amino-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)methanol (0.16 mmol, 50 mg), prepared as in Example 3 (step e) above was dissolved in tetrahydrofuran (2 mL) and triethylamine (0.299 mmol, 42 μL, 30 mg) followed by methanesulfonyl chloride (0.16 mmol, 18.4 mg) and the solution stirred at room temperature overnight. The reaction was concentrated before partitioning between dichlormethane (3 mL) and 1N HCl. (3 mL). The organic layer was collected and dried using a hydrophobic frit and concentrated under a stream of nitrogen to give a brown residue which was dissolved in DMSO (1 mL) and purified on preparative basic HPLC to give (R)—N-(5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)methanesulfonamide (18.3 mg, 0.047 mmol, 29.2%) MS (ESI): m/z [M+H]+ 390.0

Workup

  1. concentrationThe reaction was concentrated
  2. custombefore partitioning between dichlormethane (3 mL) and 1N HCl
  3. customThe organic layer was collected
  4. customdried
  5. concentrationconcentrated under a stream of nitrogen
  6. customto give a brown residue which
  7. custompurified on preparative basic HPLC

Sources & evidence

ORD record
ord-b14bc660e8c34c3cadf922ddb434bdb3
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

Loading…