Dichloromethane → HCID 20746008, compound

HRID 2308107Notes

Reaction equation

HRID 2308107 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[CH:17]=[CH:16][N:15]=[C:14]3[CH:18]=[C:19]([C:21]([N:23]4[CH2:27][CH2:26][CH:25]([O:28][CH3:29])[CH2:24]4)=[O:22])[S:20][C:13]=23)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:30])[NH:6]2.[OH-].[Na+].Cl[C:34]([O:36][C:37]1[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[CH:39][CH:38]=1)=[O:35].C(Cl)[Cl:47]>CS(C)=O.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-]>[N+:43]([C:40]1[CH:39]=[CH:38][C:37]([O:36][C:34]([N:6]2[C:7]3[C:3](=[C:2]([F:1])[C:10]([O:11][C:12]4[CH:17]=[CH:16][N:15]=[C:14]5[CH:18]=[C:19]([C:21]([N:23]6[CH2:27][CH2:26][CH:25]([O:28][CH3:29])[CH2:24]6)=[O:22])[S:20][C:13]=45)=[CH:9][CH:8]=3)[C:4]([Cl:47])=[C:5]2[CH3:30])=[O:35])=[CH:42][CH:41]=1)([O-:45])=[O:44]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 821294-Nitrophenyl chloroformateHCID 69885787HCID 69885787, compound

Product 1

HCID 20746008HCID 20746008, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred solution of [7-(4-Fluoro-2-methyl-1 h-indol-5-yloxy)-thieno[3,2-b]pyridin-2-yl]-(3-methoxy-pyrrolidin-1-yl)-methanone (399 mg, 0.94 mmole) in CH2Cl2 (30 ml) and DMSO (0.2 ml) were added, sequentially, freshly crushed NaOH (700 mg, 17.50 mmole), Bu4NBr (25 mg, catalytic amount) and 4-nitrophenyl chloroformate (1.18 g, 5.84 mmole). After stirring at ambient temperature for overnight, the reaction mixture was filtered and the filtrate was concentrated, in vacuo, to give crude product, which was further purified by flash column chromatography eluted with EtOAc : CH2Cl2:MeOH (1:1:0.02) to provide 110 mg (19%) of a yellow solid. 1H NMR (300 MHz, CDCl3): δ 8.55 (1H, d, J=5.5 Hz), 8.40 (2H, d, J=8.7 Hz), 8.04 (1H, d, J=9.1 Hz), 7.86 (1H, d, J=10.7 Hz), 7.53 (2H, d, J=9.04 Hz), 7.26 (1H, dd, J=9.2, 1.9 Hz), 6.62 (1H, d, J=5.5 Hz), 4.02-3.89 (3H, m), 3.88-3.71 (2H, m), 3.37 (3H, d, J=15.1 Hz), 2.73 (3H, s), 2.29-2.08 (2H, m).

Workup

  1. filtrationthe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated, in vacuo
  3. customto give crude product, which
  4. customwas further purified by flash column chromatography
  5. washeluted with EtOAc : CH2Cl2:MeOH (1:1:0.02)

Sources & evidence

ORD record
ord-84e64e9cd46d4b1683debad26b44854d
Source dataset
uspto-grants-2004_12
Patent number
US06833456B2

Reaction notes

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