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Methanol → 3-(1,3-Benzoxazol-2-yl)-5-[2-(4-methylpiperazin-1-yl)thiazol-5-yl]pyridin-2-amine

HRID 908392
ノート
印刷プレビュー

反応式

HRID 908392 の反応式
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:25])=[N:12][CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1.Br[C:27]1[S:31][C:30]([N:32]2[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]2)=[N:29][CH:28]=1.[F-].[Cs+].CO>C(#N)C.[Pd](Cl)Cl.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>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:25])=[N:12][CH:13]=[C:14]([C:27]2[S:31][C:30]([N:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)=[N:29][CH:28]=2)[CH:15]=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

7

反応物 4

HCID 887MethanolHCID 25953Cesium fluorideHCID 457875521-(5-Bromo-1,3-thiazol-2-yl)-4-methylpiperazineHCID 673889123-(1,3-Benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

生成物 1

HCID 673884383-(1,3-Benzoxazol-2-yl)-5-[2-(4-methylpiperazin-1-yl)thiazol-5-yl]pyridin-2-amine収率 45.8%

試薬・触媒・溶媒 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 6342Acetonitrile溶媒

反応条件

温度
120 °C

実験手順

Compound [5] was prepared as follows. 3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (150 mg), 1-(5-bromothiazol-2-yl)-4-methyl-piperazine (117 mg), bis(triphenylphosphine) palladium (II) chloride (15.61 mg) and caesium fluoride (169 mg) were weighed out in a microwave vial and sealed. Methanol (1.5 ml) was added and argon was bubbled in the resulting suspension for 10 minutes. The resulting mixture was heated in the 300 W microwave at 120° C. for 20 minutes. The crude product was purified by flash chromatography on silica gel eluting with 0 to 3% methanol in dichloromethane then 3% to 5% methanolic ammonia 7N in dichloromethane. The solvent was evaporated to dryness to afford the product, which was stirred at room temperature for 1 h in acetonitrile (3 ml), collected by filtration, washed with acetonitrile and dried under vacuum at 40° C., to give 3-(1,3-benzoxazol-2-yl)-5-[2-(4-methylpiperazin-1-yl)thiazol-5-yl]pyridin-2-amine (80 mg). NMR Spectrum: (CDCl3) 2.39 (s, 3H), 2.54-2.65 (m, 4H), 3.56-3.65 (m, 4H), 6.96 (m, 2H), 7.35 (s, 1H), 7.36-7.40 (m, 2H), 7.61 (dd, 1H), 7.74 (dd, 1H), 8.31-8.35 (m, 2H); Mass spectrum: M+H+ 393. There was no deprotection step.

後処理

  1. customsealed
  2. customargon was bubbled in the resulting suspension for 10 minutes
  3. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 3% methanol in dichloromethane
  4. customThe solvent was evaporated to dryness
  5. customto afford the product, which
  6. filtrationcollected by filtration
  7. washwashed with acetonitrile
  8. customdried under vacuum at 40° C.

出典と根拠

ORDレコード
ord-0c53394533b64608b0e638a090808824
出典データセット
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08017611B2

反応ノート

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