1-Methylpyrrolidine → HCID 25119060, compound

HRID 2261071Notes

Reaction equation

HRID 2261071 reaction equation
[CH3:1][N:2]1[CH2:11][CH:10]([C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][C:6]([OH:20])=[CH:7][CH:8]=2)[CH2:3]1.Br[C:22]1[CH:27]=[C:26]([CH2:28][N:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)[CH:25]=[CH:24][N:23]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN1CCCC1>>[CH3:1][N:2]1[CH2:11][CH:10]([C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][C:6]([O:20][C:24]3[CH:25]=[C:26]([CH2:28][N:29]4[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]4)[CH:27]=[CH:22][N:23]=3)=[CH:7][CH:8]=2)[CH2:3]1

Participants

5

Reactant 4

HCID 84541-MethylpyrrolidineHCID 10796Cesium carbonateHCID 136724712-Bromo-4-[(piperidin-1-yl)methyl]pyridineHCID 59593185HCID 59593185, compound

Product 1

HCID 25119060HCID 25119060, compoundYield 49.2%

Conditions

Temperature
150 °C

Procedure

To a Smith-process vial were added 2-methyl-4-(4-methylsulfanyl-phenyl)-1,2,3,4-tetrahydro-isoquinolin-7-ol (305.8 mg, 1.051 mmol), 2-bromo-4-piperidin-1-ylmethyl-pyridine (338.7 mg, 1.314 mmol), Cs2CO3 (684.9 mg, 2.102 mmol) and N-methylpyrrolidine (2.10 mL). The vial was purged with N2, the cap sealed, and the reaction mixture heated at 150° C. in a microwave reactor for 2 h. The mixture was diluted with Et2O, washed with 1 N NaOH, water and brine, dried, and concentrated. Purification by FCC gave the desired product (237.5 mg, 48%). MS (ESI): mass calcd. for C28H33N3OS, 459.23; m/z found, 460.3 [M+H]+. 1H NMR (acetone-d6): 8.03 (d, J=5.1, 1H), 7.23-7.19 (m, 4H), 7.04 (d, J=5.1, 1H), 6.94 (s, 1H), 6.90-6.89 (m, 1H), 6.88-6.83 (m, 2H), 4.19 (t, J=6.2, 1H), 3.63 (q, J=15.1, 2H), 3.46 (s, 2H), 2.92-2.88 (m, 1H), 2.62-2.58 (m, 1H), 2.47 (s, 3H), 2.41-2.35 (m, 4H), 2.35 (s, 3H), 1.56 (quintet, J=5.5, 4H), 1.46-1.40 (m, 2H).

Workup

  1. customThe vial was purged with N2
  2. customthe cap sealed
  3. additionThe mixture was diluted with Et2O
  4. washwashed with 1 N NaOH, water and brine
  5. customdried
  6. concentrationconcentrated
  7. customPurification by FCC

Sources & evidence

ORD record
ord-4e99bd3129874b9e966051cdbd4c41de
Source dataset
uspto-grants-2010_12
Patent number
US07846930B2

Reaction notes

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