5-Bromothieno[2,3-D]pyrimidin-4-amine → 5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}thieno[2,3-d]pyrimidin-4-amine

HRID 1909988ノート

反応式

HRID 1909988 の反応式
Br[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[S:4][CH:3]=1.[CH3:12][C:13]1[CH:14]=[C:15]([CH2:19][C:20]([N:22]2[C:30]3[C:25](=[CH:26][C:27](B4OC(C)(C)C(C)(C)O4)=[CH:28][CH:29]=3)[CH2:24][CH2:23]2)=[O:21])[CH:16]=[CH:17][CH:18]=1>O1CCOCC1.C([O-])(O)=O.[Na+].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].C(Cl)Cl>[CH3:12][C:13]1[CH:14]=[C:15]([CH2:19][C:20]([N:22]2[C:30]3[C:25](=[CH:26][C:27]([C:2]4[C:10]5[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=5[S:4][CH:3]=4)=[CH:28][CH:29]=3)[CH2:24][CH2:23]2)=[O:21])[CH:16]=[CH:17][CH:18]=1

参加物

6

反応物 2

HCID 668238985-Bromothieno[2,3-D]pyrimidin-4-amineHCID 668241231-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole

生成物 1

HCID 668236735-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}thieno[2,3-d]pyrimidin-4-amine収率 76%

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 312751,4-Dioxane溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
100 °C

実験手順

A mixture of 5-bromothieno[2,3-d]pyrimidin-4-amine (90 mg, 0.391 mmol) and 1-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (148 mg, 0.391 mmol) in 1,4-Dioxane (6 mL) and sat. aq. NaHCO3 (2 mL) was degassed with N2 for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (15.97 mg, 0.020 mmol) was added, and the reaction mixture was stirred overnight at 100° C. in a sealed vessel. The reaction was cooled down to room temperature and poured onto water. The aqueous mixture was filtered, and the solid in the filter was purified via flash chromatography on SiO2 (gradient: 100% Hexanes to 100% EtOAc) to afford the desired product (119 mg) as a white solid. LC-MS (ES) m/z=401.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 2.31 (s, 3H), 3.22 (t, J=8.46 Hz, 2H), 3.84 (s, 2H), 4.23 (t, J=8.46 Hz, 2H), 7.04-7.16 (m, 3H), 7.20-7.29 (m, 2H), 7.34 (s, 1H), 7.42 (s, 1H), 8.17 (d, J=8.34 Hz, 1H), 8.34 (s, 1H).

後処理

  1. customwas degassed with N2 for 10 minutes
  2. temperatureThe reaction was cooled down to room temperature
  3. additionpoured onto water
  4. filtrationThe aqueous mixture was filtered
  5. customthe solid in the filter was purified via flash chromatography on SiO2 (gradient: 100% Hexanes to 100% EtOAc)

出典と根拠

ORDレコード
ord-7d6bb7296de84d68b5ecfcba20127b47
出典データセット
uspto-grants-2013_12
特許番号
US08598156B2

反応ノート

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