Acetic Anhydride → 4-[1-[1-[Bis(4-fluorophenyl)methyl]piperazin-4-yl]-2-acetoxy-3-propanylthio]pyridine

HRID 1586700Notes

Reaction equation

[SH:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[CH2:16][CH:17]([OH:40])[CH2:18][N:19]1[CH2:24][CH2:23][N:22]([CH:25]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH2:21][CH2:20]1.[C:41](OC(=O)C)(=[O:43])[CH3:42]>CN(C=O)C.C(Cl)Cl.CO>[F:32][C:29]1[CH:30]=[CH:31][C:26]([CH:25]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[N:22]2[CH2:23][CH2:24][N:19]([CH2:18][CH:17]([O:40][C:41](=[O:43])[CH3:42])[CH2:16][S:1][C:2]3[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=3)[CH2:20][CH2:21]2)=[CH:27][CH:28]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To 4-mercaptopyridine (0.555 g, 5 mmol) in DMF (5 mL) with triethylamine (0.7 mL, 5 mmol) was added 1-(1-chloro-2-hydroxy-3-propanyl)-4-(4, 4'-difluorobenzhydryl) piperazine (1.91 g, 5 mmol) in DMF (15 mL) dropwise over 15 minutes under nitrogen. After 8 days, the reaction mixture was heated to 60° C. and stirred for 3 days. The DMF was removed in vacuo (1 mmHg, 60° C.) and to this crude material was added methylene chloride (5 mL), acetic anhydride (5 mmol, 0.47 mL) and triethylamine (5 mmol, 0.7 mL), and the mixture was stirred overnight. Silica gel flash chromatography using 10% methanol:methylene chloride gave an amber oil which was dissolved in methylene chloride (10 mL) and extracted with saturated sodium bicarbonate (2×20 mL), water (1×20 mL), saturated brine (1×20 mL) and dried over sodium sulfate. The solvent was removed in vacuo to give pure product (0.38 g, 15.3%); DCI/MS (M+1)= 498; 300 MHz 1H NMR (CDCl3)δ: 8.4(d,2H,J=1.25 Hz), 7.3 (m,4H), 7.2 (d,2H,J=1.4 Hz), 6.95 (m, 4H), 5.1 (m, 1H), 4.2 (s, 1H), 3.3 and 3.2 (d of d and d of d, 2H), 2.6 (d, 2H,J=6.1 Hz), 2.35 (m, 8H), 2.0 (s,3H).

Workup

customThe DMF was removed in vacuo (1 mmHg, 60° C.) and to this crude material
stirringthe mixture was stirred overnight
extractionextracted with saturated sodium bicarbonate (2×20 mL), water (1×20 mL), saturated brine (1×20 mL)
dry with materialdried over sodium sulfate
customThe solvent was removed in vacuo

Sources & evidence

ORD record: ord-8bf179eeca7a4f2fadb4200bd644a342
Source dataset: uspto-grants-1993_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05215987

Reaction notes

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