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Potassium Carbonate → N-Cyclopropyl-4-[8-(methylsulfanyl)-6-phenylimidazo[1,2-a]pyrazin-3-yl]benzamide

HRID 925593
ノート
印刷プレビュー

反応式

HRID 925593 の反応式
Br[C:2]1[N:3]=[C:4]([S:23][CH3:24])[C:5]2[N:6]([C:8]([C:11]3[CH:22]=[CH:21][C:14]([C:15]([NH:17][CH:18]4[CH2:20][CH2:19]4)=[O:16])=[CH:13][CH:12]=3)=[CH:9][N:10]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(O)CC.CN1C(=O)CCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:18]1([NH:17][C:15](=[O:16])[C:14]2[CH:21]=[CH:22][C:11]([C:8]3[N:6]4[CH:7]=[C:2]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[N:3]=[C:4]([S:23][CH3:24])[C:5]4=[N:10][CH:9]=3)=[CH:12][CH:13]=2)[CH2:20][CH2:19]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 533898994-[6-Bromo-8-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylbenzamide

生成物 1

HCID 53389900N-Cyclopropyl-4-[8-(methylsulfanyl)-6-phenylimidazo[1,2-a]pyrazin-3-yl]benzamide収率 80.5%

試薬・触媒・溶媒 4

HCID 11776Triphenylphosphine
触媒
HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒
HCID 10311-Propanol溶媒
HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
120 °C

実験手順

To a stirred solution of 4-(6-bromo-8-methylsulfanyl-imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropyl-benzamide (7.34 g, 18.2 mmol) in n-propanol (270 mL) and NMP (15 mL) was subsequently added 27.3 mL 2M potassium carbonate solution, 4.44 g phenylboronic acid (36.4 mmol, 2 eq), triphenylphosphine (238.7 mg, 0.91 mmol, 0.05 eq), 1.28 g bis(triphenylphosphin)palladium(II)chloride (1.82 mmol, 0.1 eq) in one portion at rt under argon atmosphere. After stirring for 2 h at 120° C., the mixture was concentrated in vaccuo (50% v/v), triturated with water and extracted with DCM. The organic phase was dried over sodium sulphate, filtered and the solvent was evaporated. Purification by flash chromatography (ethyl acetate/n-hexane) followed by crystallization from ethyl acetate yielded 5.87 g (80.5%)N-Cyclopropyl-4-(8-methylsulfanyl-6-phenyl-imidazo[1,2-a]pyrazin-3-yl)-benzamide: 1H-NMR (300 MHz, CDCl3): δ=8.30 (1H, s), 7.94 (4H, d), 7.77 (1H, s), 7.65 (2H, d), 7.50-7.37 (3H, m), 6.38 (1H, bs), 2.95 (1H, m), 2.80 (3H, s), 1.04 (6H, d), 0.92 (2H, m), 0.67 (2H, m) ppm.

後処理

  1. customat rt
  2. concentrationthe mixture was concentrated in vaccuo (50% v/v),
  3. customtriturated with water
  4. extractionextracted with DCM
  5. dry with materialThe organic phase was dried over sodium sulphate
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customPurification by flash chromatography (ethyl acetate/n-hexane)
  9. customfollowed by crystallization from ethyl acetate

出典と根拠

ORDレコード
ord-a6e9224dd2f3497a83a0a649e4064504
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09284317B2

反応ノート

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