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

HRID 2110741ノート

反応式

HRID 2110741 の反応式
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.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=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

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 962Water溶媒2 回HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-9d202bd06a024ff9b3f1d55f9cdf3c94
出典データセット
uspto-grants-2009_04
特許番号
US07517889B2

反応ノート

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