Sodium Carbonate → 2-(trans)-{3'-[3-(Morpholin-4-ylcarbonyl)-4-oxo-1,8-naphthyridin-1(4H)-yl]-1,1'-biphenyl-4-yl}cyclopropanecarboxylic Acid

HRID 1392713Notes

Reaction equation

HRID 1392713 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([CH:15]3[CH2:17][CH:16]3[C:18]([O:20]CC)=[O:19])=[CH:11][CH:10]=2)O1.Br[C:25]1[CH:26]=[C:27]([N:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][N:39]=3)[C:34](=[O:41])[C:33]([C:42]([N:44]3[CH2:49][CH2:48][O:47][CH2:46][CH2:45]3)=[O:43])=[CH:32]2)[CH:28]=[CH:29][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>C(O)CC.CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:44]1([C:42]([C:33]2[C:34](=[O:41])[C:35]3[C:40](=[N:39][CH:38]=[CH:37][CH:36]=3)[N:31]([C:27]3[CH:26]=[C:25]([C:9]4[CH:10]=[CH:11][C:12]([C@@H:15]5[CH2:17][C@H:16]5[C:18]([OH:20])=[O:19])=[CH:13][CH:14]=4)[CH:30]=[CH:29][CH:28]=3)[CH:32]=2)=[O:43])[CH2:45][CH2:46][O:47][CH2:48][CH2:49]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66579675Ethyl 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropanecarboxylateHCID 691580421-(3-Bromophenyl)-3-(morpholin-4-ylcarbonyl)-1,8-naphthyridin-4(1H)-one

Product 1

HCID 103456752-(trans)-{3'-[3-(Morpholin-4-ylcarbonyl)-4-oxo-1,8-naphthyridin-1(4H)-yl]-1,1'-biphenyl-4-yl}cyclopropanecarboxylic Acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86598119Dimethylformamide n-propanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of acid from step 2 (1 eq), amide from step 1 (1 eq), Na2CO3 (3.5eq.; 2M in H2O), Pd(PPh3)4 (0.15eq.) in n-propanol-DMF (1:1, 0.1M) was stirred at 80° C. for 2 h. The mixture was cooled to rt, quenched with brine and diluted with EtOAc. The organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (CHCl3:THF; 50:50), triturated in ether/acetone and then isolated by filtration to afford the title compound as a solid.

Workup

  1. temperatureThe mixture was cooled to rt
  2. customquenched with brine
  3. additiondiluted with EtOAc
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (CHCl3:THF; 50:50)
  9. customtriturated in ether/acetone
  10. customisolated by filtration

Sources & evidence

ORD record
ord-fcf3cc28118c429abf2435b29cc36e2b
Source dataset
uspto-grants-2008_03
Patent number
US07342024B2

Reaction notes

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