Sodium hydride → 2-[1-[1-[Bis(4-fluorophenyl)methyl]piperazin-4-yl]-2-hydroxy-3-propanylthio]pyridine Hemihydrate

HRID 1586699Notes

Reaction equation

HRID 1586699 reaction equation
[H-].[Na+].[SH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.Cl[CH2:11][CH:12]([OH:35])[CH2:13][N:14]1[CH2:19][CH2:18][N:17]([CH:20]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH2:16][CH2:15]1>CN(C=O)C>[OH2:35].[F:27][C:24]1[CH:25]=[CH:26][C:21]([CH:20]([C:28]2[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=2)[N:17]2[CH2:16][CH2:15][N:14]([CH2:13][CH:12]([OH:35])[CH2:11][S:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=3)[CH2:19][CH2:18]2)=[CH:22][CH:23]=1.[F:34][C:31]1[CH:30]=[CH:29][C:28]([CH:20]([N:17]2[CH2:16][CH2:15][N:14]([CH2:13][CH:12]([OH:35])[CH2:11][S:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=3)[CH2:19][CH2:18]2)[C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 103851541-(1-Chloro-2-hydroxy-3-propanyl)-4-(4,4'-difluorobenzhydryl)piperazineHCID 178418616HCID 178418616, compound

Product 1

HCID 881286982-[1-[1-[Bis(4-fluorophenyl)methyl]piperazin-4-yl]-2-hydroxy-3-propanylthio]pyridine Hemihydrate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To NaH (10 mmol, 0.48 g, pentane washed) in DMF (10 mL) was added 2-mercaptopyridine (10 mmol, 1.11 g) at 0° C. After stirring for 2 hours at 0° C., 1-(1-chloro-2-hydroxy-3-propanyl)-4-(4, 4'-difluorobenzhydryl)piperazine (5 mmol, 1.91 g) in DMF (20 mL) was added dropwise under nitrogen over 10 minutes. The mixture was stirred 15 minutes at 0° C. and 5 days at room temperature. The mixture was then filtered and the filtrate concentrated in vacuo (1 mmHg, 70° C.). The concentrated mixture was purified on a silica gel column using 5% methanol:methylene chloride. Crude material thus obtained was rechromatographed on silica gel using 10% acetone:methylene chloride and then 10% methanol:methylene chloride. After drying in a vacuum dessicator overnight, the pure product was an amber glass (0.87 g, 38.1%); DCI MS (M+1)=456; (300 MHz) 1H NMR (CDCl3)δ:8.4 (d,1H) and 7.5 (m,1H), 7.3 (m,4H), 7.25 (m,1H), 7.0 (m,5H), 4.0 (m, 1H), 3.2-3.6 (m,4H), 2.5 (m,10H).

Workup

  1. stirringThe mixture was stirred 15 minutes at 0° C. and 5 days at room temperature
  2. filtrationThe mixture was then filtered
  3. concentrationthe filtrate concentrated in vacuo (1 mmHg, 70° C.)
  4. customThe concentrated mixture was purified on a silica gel column
  5. customCrude material thus obtained
  6. customwas rechromatographed on silica gel using 10% acetone
  7. customAfter drying in a vacuum dessicator overnight

Sources & evidence

ORD record
ord-17e0b201f32943fd8cec93dde9571d31
Source dataset
uspto-grants-1993_06
Patent number
US05215987

Reaction notes

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