Cesium carbonate → 2-(3-{2-Methoxy-6-[(thiophen-3-ylmethyl)-amino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid

HRID 216213

반응식

HRID 216213 반응식
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][C:12]2[CH:16]=[CH:15][S:14][CH:13]=2)[CH:3]=1.[C:17]([C:20]([C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1)([CH3:22])[CH3:21])([OH:19])=[O:18].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.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>[CH3:9][O:8][C:6]1[N:7]=[C:2]([C:25]2[CH:24]=[C:23]([C:20]([CH3:22])([CH3:21])[C:17]([OH:19])=[O:18])[CH:28]=[CH:27][CH:26]=2)[CH:3]=[C:4]([NH:10][CH2:11][C:12]2[CH:16]=[CH:15][S:14][CH:13]=2)[N:5]=1

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 86615704(6-Chloro-2-methoxy-pyrimidin-4-yl)-thiophen-3-ylmethyl-amine

생성물 1

HCID 116106622-(3-{2-Methoxy-6-[(thiophen-3-ylmethyl)-amino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid수율 4.7%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
90 °C

실험 절차

Argon is bubbled through a mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-thiophen-3-ylmethyl-amine (216 mg, 0.84 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl boronic acid [312 mg, 1.5 mmol, see Example 49(b) step 2], Cs2CO3 (821 mg, 2.52 mmol), and tetrakis(triphenylphosphine)palladium (0) (92 mg, 0.08 mmol) in ethylene glycol dimethyl ether (2.5 mL) and water (0.5 mL), for a period of 10 minutes. The reaction vessel is sealed and heated to 90° C. After stirring for 6 hours the heating is turned off and the mixture is allowed to cool to ambient temperature upon standing for 24 hours. The mixture is diluted with water (40 mL) and extracted twice with EtOAc (25 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and concentrated to afford 2-(3-{2-methoxy-6-[(thiophen-3-ylmethyl)-amino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [15 mg, 4.6%, Example 71] as a solid. LCMS RT=1.94 minutes, MS: 384 (M+H). IC50=393 nM

후처리

  1. customThe reaction vessel is sealed
  2. temperatureto cool to ambient temperature
  3. waitupon standing for 24 hours
  4. extractionextracted twice with EtOAc (25 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-1367907502564fb29e52e843d0d39a2a
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193183B2

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