1-Hydroxybenzotriazole → HCID 18700143, compound

HRID 2289339Notes

Reaction equation

HRID 2289339 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22](O)=[O:23])=[C:17]([O:25][CH2:26][C:27]([F:30])([F:29])[F:28])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:31]1[CH2:36][CH2:35][CH:34]([N:37]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[CH2:40][CH2:39][C:38]2=[O:47])[CH2:33][CH2:32]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)CCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22]([N:31]3[CH2:36][CH2:35][CH:34]([N:37]4[C:46]5[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=5)[CH2:40][CH2:39][C:38]4=[O:47])[CH2:33][CH2:32]3)=[O:23])=[C:17]([O:25][CH2:26][C:27]([F:30])([F:29])[F:28])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 107281851-(piperidin-4-yl)-3,4-dihydroquinolin-2(1H)-oneHCID 15840441HCID 15840441, compound

Product 1

HCID 18700143HCID 18700143, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-(N-tert-butyloxy-carbonyl-4-piperidinyloxy)-2-(2,2,2-trifluoroethoxy)phenylacetic acid from Step 8 of Example 1 and 1-(piperidin-4-yl)-3,4-dihydroquinolin-2(1H)-one prepared by the method of Ogawa, et al., J. Med. Chem. (1993), vol. 36, pp. 2011-2017) in DMF was added HOBT, EDC, and DIEA. The solution was stirred at ambient temperature for 14 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (100 mL) and 0.25 M aqueous citric acid (75 mL). The organic phase was separated and washed with H2O (25 mL), saturated aqueous NaHCO3 (75 mL), and brine (25 mL). The organic phase was dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using EtOAc as eluant. The product-containing fractions were evaporated under reduced pressure to give 1-(1-(4-(N-tert-butyloxycarbonyl-4-piperidinyloxy)-2-(2,2,2-trifluoroethoxy)phenylacetyl)piperidin-4-yl)-3,4-dihydro-quinolin-2(1H)-one as an amorphous solid (HPLC retention time=10.8 min (method A); TLC Rf=0.7 (EtOAc)).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was partitioned between EtOAc (100 mL) and 0.25 M aqueous citric acid (75 mL)
  3. customThe organic phase was separated
  4. washwashed with H2O (25 mL), saturated aqueous NaHCO3 (75 mL), and brine (25 mL)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customThe residue was purified by pressurized silica gel column chromatography
  9. customThe product-containing fractions were evaporated under reduced pressure

Sources & evidence

ORD record
ord-9eed8e8273524e72923476b1eabf41c4
Source dataset
uspto-grants-2000_07
Patent number
US06090805

Reaction notes

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