Diisopropylethylamine → HCID 16678993, compound

HRID 2103418Notes

Reaction equation

HRID 2103418 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][C:7]2([OH:13])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[Cl:16][C:17]1[C:18]([C:27]([F:30])([F:29])[F:28])=[N:19][N:20]([CH2:23][C:24](O)=[O:25])[C:21]=1[CH3:22].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CC(N(C)C)=O.CCOC(C)=O>[Cl:16][C:17]1[C:18]([C:27]([F:29])([F:28])[F:30])=[N:19][N:20]([CH2:23][C:24]([N:10]2[CH2:9][CH2:8][C:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:15][CH:14]=3)([OH:13])[CH2:12][CH2:11]2)=[O:25])[C:21]=1[CH3:22]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1876853(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acidHCID 2724699PyBOPHCID 104886244-[(4-Fluorophenyl)methyl]piperidin-4-ol

Product 1

HCID 16678993HCID 16678993, compoundYield 80.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a 20 mL vial equipped with a magnetic stirring bar was added 78 mg of 4-(4-Fluoro-benzyl)-piperidin-4-ol (0.37 mmol, 1.0 equiv.), 100 mg of (4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid (0.41 mmol, 1.1 equiv), and 207 mg of (Benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (0.40 mmol, 1.1 equiv.). The reagents were dissolved in 3 mL of DMA and to the resultant solution was added 0.26 mL of DIPEA (1.5 mmol, 4.1 equiv). The reaction solution was stirred for 5 h and then poured into 50 mL of EtOAc. The organic phase was washed with saturated aq. NaCl (5×10 mL), 1% aq NaOH (1×10 mL), and 0.1 N HCl (1×10 mL). The organic phase was then dried over MgSO4 and concentrated in vacuo to afford a yellow oil, which was purified by preparative HPLC to afford 129 mg of 2-(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-1-[4-(4-fluoro-benzyl)-4-hydroxy-piperidin-1-yl]-ethanone (80% yield): MS (ES) M+H expected=414.2, found 414.2. 1H NMR (CDCl3, 400 MHz, 23° C.) δ 7.10-7.14 (m, 2H), 6.99-7.03 (m, 2H), 5.00 (d, J=15.6 Hz, 1H), 4.86 (d, J=15.6 Hz, 1H), 4.32-4.35 (m, 1H), 3.64-6.68 (m, 1H), 3.42-3.50 (m, 1H), 2.96-3.03 (m, 1H), 2.74 (s, 2H), 2.26 (s, 3H), 1.55-1.61 (m, 4H), 1.23 (s, 1H).

Workup

  1. customTo a 20 mL vial equipped with a magnetic stirring bar
  2. washThe organic phase was washed with saturated aq. NaCl (5×10 mL), 1% aq NaOH (1×10 mL), and 0.1 N HCl (1×10 mL)
  3. dry with materialThe organic phase was then dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customto afford a yellow oil, which
  6. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-a6031005f6fe4c17add53f81dc1930e2
Source dataset
uspto-grants-2009_08
Patent number
US07576106B2

Reaction notes

Loading…