1-Hydroxybenzotriazole → HCID 53476794, compound

HRID 245228Notes

Reaction equation

HRID 245228 reaction equation
[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[C:15]([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=4)=[N:16][C:17]4[C:22]([C:23]=3[C:24](O)=[O:25])=[CH:21][CH:20]=[C:19]([S:27]([CH3:30])(=[O:29])=[O:28])[CH:18]=4)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:41]1([C@@H:47]([NH2:49])[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>CN(C)C=O.ClCCCl>[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[C:15]([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:38])[F:39])[CH:32]=4)=[N:16][C:17]4[C:22]([C:23]=3[C:24]([NH:49][C@H:47]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH3:48])=[O:25])=[CH:21][CH:20]=[C:19]([S:27]([CH3:30])(=[O:28])=[O:29])[CH:18]=4)[CH2:9][CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 758181-Phenethylamine, (-)-HCID 81531DiisopropylethylamineHCID 67383919HCID 67383919, compound

Product 1

HCID 53476794HCID 53476794, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(1,4′-bipiperidin-1′-ylmethyl)-7-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.100 g, 0.174 mmol), (1S)-1-phenylethanamine (0.032 g, 0.261 mmol), EDC (0.167 g, 0.869 mmol), HOBT (0.027 g, 0.174 mmol), and N,N-diisopropylethylamine (0.303 mL, 1.74 mmol) in N,N-dimethylformamide (2 mL) and 1,2-dichloroethane (2 mL) was stirred at room temperature overnight before it was heated to 50° C. for 4 h. The solvent was removed under reduced pressure. The residue was dissolved in DMSO and purified via HPLC (Waters, 30-80% MeCN/H2O with 0.1% TFA). The fractions containing the product were neutralized with saturated aqueous NaHCO3, acetonitrile was removed under reduced pressure, and the residue was diluted with water. The solid material was collected by filtration, washed with water, and air dried to afford 3-(1,4′-bipiperidin-1′-ylmethyl)-7-(methylsulfonyl)-N-[(1S)-1-phenylethyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (0.086 g, 73% yield). MS (m/z) 679.3 (M+H+).

Workup

  1. temperaturewas heated to 50° C. for 4 h
  2. customThe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in DMSO
  4. custompurified via HPLC (Waters, 30-80% MeCN/H2O with 0.1% TFA)
  5. additionThe fractions containing the product
  6. customwas removed under reduced pressure
  7. additionthe residue was diluted with water
  8. filtrationThe solid material was collected by filtration
  9. washwashed with water, and air
  10. customdried

Sources & evidence

ORD record
ord-c5c0fe30038d4b37be6397eb690e36bd
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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