Trimethylsilylacetylene → 4-{2-ethoxy-6-[2-(trimethylsilyl)ethynyl]-1H-1,3-benzodiazol-1-yl}pyrimidin-2-amine

HRID 1398645ノート

反応式

HRID 1398645 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([O:10][CH2:11][CH3:12])[N:7]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=3)[C:6]=2[CH:20]=1.[C:21]([Si:23]([CH3:26])([CH3:25])[CH3:24])#[CH:22]>N1CCCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH2:11]([O:10][C:8]1[N:7]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=2)[C:6]2[CH:20]=[C:2]([C:22]#[C:21][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:3]=[CH:4][C:5]=2[N:9]=1)[CH3:12]

参加物

6

反応物 2

HCID 66111Trimethylsilylacetylene2 回HCID 681818044-(6-Bromo-2-ethoxy-1,3-benzodiazol-1-yl)pyrimidin-2-amine

生成物 1

HCID 681816194-{2-ethoxy-6-[2-(trimethylsilyl)ethynyl]-1H-1,3-benzodiazol-1-yl}pyrimidin-2-amine

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒2 回HCID 178418397HCID 178418397、化合物触媒2 回HCID 8082Piperidine溶媒

反応条件

温度
65 °C

実験手順

To a solution of 4-(6-bromo-2-ethoxy-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine (270 mg, 0.74 mmol) in piperidine (1.8 mL) was introduced tetrakis(triphenylphosphine)palladium(0) (69 mg, 0.06 mmol), copper(I) iodide (11 mg, 0.06 mmol) and ethynyltrimethylsilane (0.53 mL, 3.71 mmol). The reaction mixture was warmed to 65° C. for 3 hr. After cooling to RT, the reaction mixture was re-treated with further tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.01 mmol), copper(I) iodide (5 mg, 0.03 mmol), ethynyltrimethylsilane (0.20 mL, 1.4 mmol) and warmed to 65° C. for an additional 2 hr. The reaction mixture was concentrated in vacuo and the residue re-dissolved in DCM (10 mL) and re-evaporated to dryness in vacuo (this procedure was repeated twice). Purification of the residue by column chromatography (Biotage, DCM containing a 2-8% gradient of methanol) furnished the title compound as an off-white solid: 1H NMR (250 MHz, DMSO) delta −0.07-0.07 (9 H, m), 1.21 (3H, t, J=7.01 Hz), 4.40 (2H, q, J=7.06 Hz), 6.65-6.81 (1H, m), 6.88 (2H, br. s.), 7.06 (1H, dd, J=8.15, 1.60 Hz), 7.20 (1H, d, J=8.22 Hz), 7.98 (1H, d, J=1.22 Hz), 8.12-8.25 (1H, m); LCMS: m/z=+352.45 (M+H)+.

後処理

  1. temperatureAfter cooling to RT
  2. temperaturewarmed to 65° C. for an additional 2 hr
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. dissolutionthe residue re-dissolved in DCM (10 mL)
  5. customre-evaporated to dryness in vacuo (this procedure
  6. customPurification of the residue by column chromatography (Biotage, DCM containing a 2-8% gradient of methanol)

出典と根拠

ORDレコード
ord-236d2508d5f1491e9d73a51f28cb33d2
出典データセット
uspto-grants-2014_12
特許番号
US08901313B2

反応ノート

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