Cesium carbonate → 3-{3-tert-Butylsulfanyl-5-(6-fluoro-quinolin-2-ylmethoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl ester

HRID 2370404Notes

Reaction equation

HRID 2370404 reaction equation
[CH2:1]([O:3][C:4](=[O:39])[C:5]([CH3:38])([CH3:37])[CH2:6][C:7]1[N:8]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=3)=[CH:25][CH:24]=2)[C:9]2[C:14]([C:15]=1[S:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][C:12]([OH:21])=[CH:11][CH:10]=2)[CH3:2].Br[CH2:41][C:42]1[CH:51]=[CH:50][C:49]2[C:44](=[CH:45][CH:46]=[C:47]([F:52])[CH:48]=2)[N:43]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N>[CH2:1]([O:3][C:4](=[O:39])[C:5]([CH3:38])([CH3:37])[CH2:6][C:7]1[N:8]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([C:29]3[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=3)=[CH:27][CH:28]=2)[C:9]2[C:14]([C:15]=1[S:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[CH:13][C:12]([O:21][CH2:41][C:42]1[CH:51]=[CH:50][C:49]3[C:44](=[CH:45][CH:46]=[C:47]([F:52])[CH:48]=3)[N:43]=1)=[CH:11][CH:10]=2)[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 216180422-(Bromomethyl)-6-fluoroquinolineHCID 592488773-[5-Hydroxy-3-(2-methyl-2-propylthio)-1-[4-(2-methoxypyrid-5-yl)benzyl]indol-2-yl]-2,2-dimethylpropionic acid ethyl ester

Product 1

HCID 568496983-{3-tert-Butylsulfanyl-5-(6-fluoro-quinolin-2-ylmethoxy)-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl esterYield 90.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 3-{3-tert-Butylsulfanyl-5-hydroxy-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl ester (D-2; 6.5 g, 11.9 mmol) in MeCN (75 mL) was added 2-bromomethyl-6-fluoro-quinoline (3.14 g, 13.1 mmol), and Cs2CO3 (9.7 g, 29.8 mmol). The reaction was stirred at room temperature overnight, after which LCMS showed the reaction was complete. The reaction mixture was partitioned between EtOAc and water, the aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified on silica gel (0 to 25% EtOAc in hexanes) to give the desired product (D-3, 7.6 g).

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. extractionthe aqueous layer was extracted with EtOAc
  3. dry with materialthe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on silica gel (0 to 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-544fcbd77cda4623b0b1e5b30af6db4b
Source dataset
uspto-grants-2014_04
Patent number
US08710081B2

Reaction notes

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