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Cesium carbonate → 4-{6-[2-Fluoro-4-(2-methanesulfonyl-ethoxy)-phenylamino]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid Isopropyl Ester

HRID 2377904
Notes
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Reaction equation

HRID 2377904 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([NH:21][C:22]3[CH:27]=[CH:26][C:25](I)=[CH:24][C:23]=3[F:29])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:36][S:37]([CH2:40][CH2:41][OH:42])(=[O:39])=[O:38]>[Cu](I)I>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([O:42][CH2:41][CH2:40][S:37]([CH3:36])(=[O:39])=[O:38])=[CH:24][C:23]=3[F:29])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 848342-(Methylsulfonyl)ethanolHCID 598568514-[6-(2-Fluoro-4-iodo-phenylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester

Product 1

HCID 598566564-{6-[2-Fluoro-4-(2-methanesulfonyl-ethoxy)-phenylamino]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid Isopropyl EsterYield 3%

Reagents, catalysts & solvents 1

HCID 83717Copper iodideCatalyst

Conditions

Temperature
150 °C

Procedure

General procedure of coupling alcohol to aryl halides: A mixture of 4-[6-(2-fluoro-4-iodo-phenylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester (103 mg, 0.2 mmole), cesium carbonate (130 mg, 0.4 mmole), copper iodide (8 mg, 0.04 mmole), and 1, 10-phenanthroline (14 mg, 0.08 mmole) in 2-methanesulfonyl-ethanol (3 mL) was heated under microwave irradiation at 150° C. for 1 hour. The crude mixture was purified by HPLC to provide Compound A95 as a yellow solid (3 mg, 3%). Exact mass calculated for C23H31FN4O6S 510.2, found 511.3 (MH+).

Workup

  1. customThe crude mixture was purified by HPLC

Sources & evidence

ORD record
ord-22448c79159e4e19a6a2db77f9cbbc13
Source dataset
uspto-grants-2008_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07470699B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes