Trifluoroacetic acid → HCID 11342085, compound

HRID 33585Notes

Reaction equation

HRID 33585 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][C:18]2[N:21]([CH2:31][CH:32]([OH:48])[CH2:33][N:34]3[CH2:39][CH2:38][N:37]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=4[C:46]#[N:47])[CH2:36][CH2:35]3)[N:22]=[C:23]([C:24]3[CH:29]=[CH:28][C:27]([I:30])=[CH:26][CH:25]=3)[C:17]=2[CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[OH:48][CH:32]([CH2:31][N:21]1[C:18]2[CH2:19][CH2:20][NH:15][CH2:16][C:17]=2[C:23]([C:24]2[CH:29]=[CH:28][C:27]([I:30])=[CH:26][CH:25]=2)=[N:22]1)[CH2:33][N:34]1[CH2:35][CH2:36][N:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[C:46]#[N:47])[CH2:38][CH2:39]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 10146441HCID 10146441, compound

Product 1

HCID 11342085HCID 11342085, compoundYield 100.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (3 mL) was added to a solution of 1-{3-[4-(2-cyano-phenyl)-piperazin-1-yl]-2-hydroxy-propyl}-3-(4-iodo-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (0.402 g, 0.601 mmol) in CH2Cl2 (3 mL) and the reaction mixture was stirred for 2 h. The mixture was concentrated, then diluted with EtOAc. The organic layer was washed with aqueous NaHCO3 and brine, dried (Na2SO4), and concentrated to afford the amine (0.342 g, 100%) as a yellowish foam. TLC (silica, 10% acetone/CH2Cl2): Rf=0.14. MS (electrospray): m/z 569.2 (569.1, calculated for C26H29IN6O, [M+H]+). 1H NMR (400 MHz, CDCl3:CD3OD(6:1)): 7.73 (d, J=8.6 Hz, 2H), 7.56 (dd, J=7.6, 1.8 Hz, 1H), 7.52 (t, J=8.0 Hz, 1H), 7.25 (d, J=8.6 Hz, 2H), 7.09 (t, J=7.6 Hz, 1H), 7.02 (dd, J=8.4 Hz, 1H), 4.43-4.36 (m, 1H), 4.31 (s, 2H), 4.21 (dd, J=14.1, 4.5 Hz, 1H), 4.11 (dd, J=14.5, 6.3 Hz, 1H), 3.54-3.49 (m, 2H), 3.40-3.24 (m, 8H), 3.18-3.06 (m, 3H), 3.03-2.95 (m, 3H). B. 1-{3-[4-(2-Cyano-phenyl)-piperazin-1-yl]-2-hydroxy-propyl}-3-(4-iodo-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid amide. Diisopropylethylamine (0.531 mL, 3.05 mmol), DMAP (5 mg), and trimethylsilyl isocyanate (0.413 mL, 3.05 mmol) were added to a solution of 2-(4-{2-hydroxy-3-[3-(4-iodo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-benzonitrile in pyridine (3 mL) and CH2Cl2 (6 mL). The reaction mixture was stirred for 20 h, then partitioned between aqueous NaHCO3 and CH2Cl2. The CH2Cl2 layer was washed with brine, dried (Na2SO4), and concentrated. The resulting product was dissolved in CH2Cl2 (5 mL) and treated with 21 wt % sodium ethoxide in EtOH (0.5 mL) for 3 h. The reaction mixture was washed with brine, dried (Na2SO4), and concentrated. Purification by column chromatography (silica, 0-10% MeOH/CH2Cl2) afforded 290 mg (78%) of the title compound. HPLC (reverse phase conditions), tR=4.21 min. MS (electrospray): m/z 612.2 (612.5, calculated for C27H30IN7O2, M++H). 1H NMR (400 MHz, CDCl3): 7.73 (d, J=8.6 Hz, 2H), 7.57 (dd, J=7.6, 1.6 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.36 (d, J=8.6 Hz, 2H), 7.05 (t, J=7.6 Hz, 1H), 7.00 (d, J=8.4 Hz, 1H), 4.64 (br s, 2H), 4.57 (br s, 2H), 4.30 (br s, 1H), 4.20 (dd, J=14.1, 3.3 Hz, 1H), 4.06 (dd, J=14.1, 6.3 Hz, 1H), 3.82-3.65 (m, 2H), 3.29-3.20 (m, 4H), 3.04-2.80 (m, 6H), 2.68 (br s, 2H).

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with EtOAc
  3. washThe organic layer was washed with aqueous NaHCO3 and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-59a6423fadf2444b94284a3b64cb8aef
Source dataset
uspto-grants-2008_09
Patent number
US07429591B2

Reaction notes

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