Quinoline-3-boronic acid → HCID 46191629, compound

HRID 336891Notes

Reaction equation

HRID 336891 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[NH:12][C:13](=[O:42])[CH2:14][N:15]([C:16]4[CH:21]=[CH:20][C:19]([N:22]5[CH2:27][CH2:26][CH:25]([C:28]([NH:30][CH:31]6[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]6)=[O:29])[CH2:24][CH2:23]5)=[C:18]([C:38]([F:41])([F:40])[F:39])[CH:17]=4)[C:5]=3[C:4]=2[CH:3]=1.[N:43]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH:46]=[C:45](B(O)O)[CH:44]=1.CC(C1C=C(C(C)C)C(C2C(P(C(C)(C)C)C(C)(C)C)=CC=CC=2)=C(C(C)C)C=1)C>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:37][N:34]1[CH2:33][CH2:32][CH:31]([NH:30][C:28]([CH:25]2[CH2:24][CH2:23][N:22]([C:19]3[CH:20]=[CH:21][C:16]([N:15]4[C:5]5[C:4]6[CH:3]=[C:2]([C:45]7[CH:44]=[N:43][C:52]8[C:47]([CH:46]=7)=[CH:48][CH:49]=[CH:50][CH:51]=8)[CH:11]=[CH:10][C:9]=6[N:8]=[CH:7][C:6]=5[NH:12][C:13](=[O:42])[CH2:14]4)=[CH:17][C:18]=3[C:38]([F:41])([F:40])[F:39])[CH2:27][CH2:26]2)=[O:29])[CH2:36][CH2:35]1

Participants

6

Reactant 3

HCID 2734663Quinoline-3-boronic acidHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 585250731-(4-(9-bromo-3-oxo-3,4-dihydropyrazino[2,3-c]quinolin-1(2H)-yl)-2-(trifluoromethyl)phenyl)-N-(1-methylpiperidin-4-yl)piperidine-4-carboxamide

Product 1

HCID 46191629HCID 46191629, compoundYield 3.1%

Reagents, catalysts & solvents 2

HCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 8.5 1-(4-(9-bromo-3-oxo-3,4-dihydropyrazino[2,3-c]quinolin-1(2H)-yl)-2-(trifluoromethyl)phenyl)-N-(1-methylpiperidin-4-yl)piperidine-4-carboxamide (46 mg, 0.07 mmol, 1 equiv.) in dioxane (2 mL) and 1N sodium carbonate solution (0.6 mL) in a sealed tube at room temperature was added 7 quinolin-3-yl-boronic acid (24 mg, 0.14 mmol, 2 equiv.), t-butyl-Xphos (3 mg, 0.007 mmol, 0.1 equiv.), and PdCl2(Ph3P)2 (4.9 mg, 0.007 mmol, 0.1 equiv.). The resulting mixture was degassed, sealed and heated overnight to 100° C. Upon cooling to room temperature, the reaction mixture was filtered through celite and washed with EtOAc (2 mL). The collected solution was evaporated and the residue was purified via HPLC to afford the desired product 8.6 N-(1-methylpiperidin-4-yl)-1-(4-(3-oxo-9-(quinolin-3-yl)-3,4-dihydropyrazino[2,3-c]quinolin-1(2H)-yl)-2-(trifluoromethyl)phenyl)piperidine-4-carboxamide 1.5 mg. LC-MS: (M+H) 694.40

Workup

  1. customThe resulting mixture was degassed
  2. customsealed
  3. temperatureheated overnight to 100° C
  4. filtrationthe reaction mixture was filtered through celite
  5. washwashed with EtOAc (2 mL)
  6. customThe collected solution was evaporated
  7. customthe residue was purified via HPLC

Sources & evidence

ORD record
ord-e08b0e7f95a74409a636b3e47e9ae0f4
Source dataset
uspto-grants-2014_11
Patent number
US08889706B2

Reaction notes

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