(Diethylamino)sulfur trifluoride → 2-(4-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-fluoro-propyl}-piperazin-1-yl)-benzonitrile

HRID 132902Notes

Reaction equation

HRID 132902 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][C:7]2[N:10]([CH2:23][CH:24](O)[CH2:25][N:26]3[CH2:31][CH2:30][N:29]([C:32]4[CH:39]=[CH:38][CH:37]=[CH:36][C:33]=4[C:34]#[N:35])[CH2:28][CH2:27]3)[N:11]=[C:12]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)[C:6]=2[CH2:5]1)(=[O:3])[CH3:2].CCN(S(F)(F)[F:47])CC.CO.C(Cl)Cl>C(Cl)Cl>[C:1]([N:4]1[CH2:9][CH2:8][C:7]2[N:10]([CH2:23][CH:24]([F:47])[CH2:25][N:26]3[CH2:31][CH2:30][N:29]([C:32]4[CH:39]=[CH:38][CH:37]=[CH:36][C:33]=4[C:34]#[N:35])[CH2:28][CH2:27]3)[N:11]=[C:12]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)[C:6]=2[CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 103028372-(4-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperazin-1-yl)-benzonitrileHCID 21226129Dichloromethane methanol

Product 1

HCID 102809672-(4-{3-[5-Acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-fluoro-propyl}-piperazin-1-yl)-benzonitrileYield 50.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-(4-{3-[5-acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperazin-1-yl)-benzonitrile (150 mg, 0.27 mmol) in CH2Cl2 (1 mL) was treated with DAST (Et2NSF3, 7 μL, 0.60 mmol) at −78° C. The reaction mixture was slowly warmed to 25° C. for 1 h and then to 60° C. for an additional 2 h. Preparative TLC (silica, 5% MeOH/CH2Cl2) provided 75 mg (50%) of the title compound as a light yellow powder. TLC (5% MeOH/CH2Cl2): Rf=0.28. MS (electrospray): m/z 555.2 ([M+H]+, C29H30F4N6O requires 554.2). 1H NMR (CDCl3, 400 MHz, a mixture of two rotamers): 7.71 and 7.59 (AB pattern, Jab=8.2 Hz, 2H), 7.66 and 7.62 (AB pattern, Jab=8.4 Hz, 2H), 7.50-7.38 (m, 2H), 6.96-6.92 (m, 2H), 5.01 (dp, J=49.0, 3.0 Hz, 1H), 4.77 and 4.73 (AB pattern, Jab=15.7 Hz, 1.1H), 4.59 (s, 0.9H), 4.41-4.18 (m, 2H), 3.95-3.80 (m, 1H), 3.69 (dd, J=5.5, 5.5 Hz, 1H), 3.18 (m, 4H), 2.83-2.65 (m, 8H), 2.14 (s, 1.6H), 2.10 (s, 1.4H).

Sources & evidence

ORD record
ord-19c9e8c71e83416dbb5eaefa238435bf
Source dataset
uspto-grants-2008_06
Patent number
US07388011B2

Reaction notes

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