Water → 4-(6-Methoxy-4-methylquinazolin-2-yl)benzoic acid

HRID 1472675

反応式

HRID 1472675 の反応式
Cl[C:2]1[N:11]=[C:10]([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.[C:15]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)([OH:17])=[O:16].C([O-])([O-])=O.[K+].[K+].O>COCCOCCO.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:14][O:13][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([C:21]1[CH:22]=[CH:23][C:18]([C:15]([OH:17])=[O:16])=[CH:19][CH:20]=1)[N:11]=[C:10]2[CH3:12]

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 579701842-Chloro-6-methoxy-4-methylquinazoline2 回

生成物 1

HCID 679750294-(6-Methoxy-4-methylquinazolin-2-yl)benzoic acid収率 78%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 49835946Degme H2O溶媒

反応条件

温度
120 °C

実験手順

To a mixture of 2-chloro-6-methoxy-4-methylquinazoline (Intermediate 9, 350 mg, 1.68 mmol), 4-carboxyphenylboronic acid (418 mg, 2.52 mmol), and K2CO3 (464 mg, 3.36 mmol) in DEGME/H2O (7 mL/1 mL) was added Pd(dppf)Cl2 (30.2 mg, 0.0369 mmol) under N2 atmosphere. Then the mixture was heated to 120° C. for 2 hours. To the reaction mixture was added H2O (30 mL), extracted with EtOAc (15 mL×2), the aqueous layer was acidified with 1M HCl to pH=1-2, filtered and the filter cake was washed with MeOH and dried under high vacuum to give the product (380 mg, yield 78%). 1H NMR (DMSO-d6 400 MHz): δ 8.61 (d, J=8.0 Hz, 2H), 8.10 (d, J=8.4 Hz, 2H), 7.99 (d, J=9.2 Hz, 1H), 7.65 (dd, J=9.2, 2.8 Hz, 1H), 7.54 (d, J=2.8 Hz, 1H), 3.98 (s, 3H), 2.99 (s, 3H).

後処理

  1. extractionextracted with EtOAc (15 mL×2)
  2. filtrationfiltered
  3. washthe filter cake was washed with MeOH
  4. customdried under high vacuum

出典と根拠

ORDレコード
ord-041b0ecd9802421ab328958e89fad29e
出典データセット
uspto-grants-2015_04
特許番号
US09012646B2

関連ノート

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