Dichloromethane → 2-(4-{3-[3-(4-Chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperazin-1-yl)-benzonitrile

HRID 500949Notes

Reaction equation

HRID 500949 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH2:25][CH:26]([OH:42])[CH2:27][N:28]3[CH2:33][CH2:32][N:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[C:40]#[N:41])[CH2:30][CH2:29]3)[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH3:24])[CH:18]=3)[C:10]=2[CH2:9]1)=O)(C)(C)C.C(Cl)Cl>FC(F)(F)C(O)=O>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([C:16]2[C:10]3[CH2:9][NH:8][CH2:13][CH2:12][C:11]=3[N:14]([CH2:25][CH:26]([OH:42])[CH2:27][N:28]3[CH2:33][CH2:32][N:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[C:40]#[N:41])[CH2:30][CH2:29]3)[N:15]=2)=[CH:18][C:19]=1[CH3:24]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 684621993-(4-Chloro-3-methyl-phenyl)-1-{3-[4-(2-cyano-phenyl)-piperazin-1-yl]-2-hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 179754122-(4-{3-[3-(4-Chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperazin-1-yl)-benzonitrileYield 100.4%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

3-(4-Chloro-3-methyl-phenyl)-1-{3-[4-(2-cyano-phenyl)-piperazin-1-yl]-2-hydroxy-propyl}-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (1.26 g, 2.13 mmol) was dissolved in trifluoroacetic acid (3 mL) and CH2Cl2 (3 mL) and allowed to stir for 2 h. The reaction mixture was concentrated, taken up in EtOAc (50 mL) and washed with aqueous NaHCO3 (2×25 mL). The EtOAc layer was dried over Na2SO4 and concentrated to give 2-(4-{3-[3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperazin-1-yl)-benzonitrile (1.05 g, 99%) as a yellow foam. TLC (silica, 10% MeOH/CH2Cl2): Rf=0.27. MS (electrospray): m/z 491.2 (491.2, calculated for C27H31ClN6O, [M+H]+). 1H NMR (400 MHz, CDCl3): 9.8 (br s, 1H), 7.55 (d, J=7.6 Hz, 1H), 7.50 (t, J=8.2 Hz, 1H), 7.38 (s, 1H), 7.31 (d, J=8.2 Hz, 1H), 7.20 (d, J=8.2 Hz, 1H), 7.11 (t, J=8.2 Hz, 1H), 6.98 (d, J=8.2 Hz, 1H), 4.56 (br s, 1H), 4.12-4.32 (m, 4H), 2.98-3.51 (m, 13H), 2.35 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washwashed with aqueous NaHCO3 (2×25 mL)
  3. dry with materialThe EtOAc layer was dried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-3012e2ebd01d4288b126b3fb57ae2a00
Source dataset
uspto-grants-2010_08
Patent number
US07772236B2

Reaction notes

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