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

HRID 1398645노트

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HRID 1398645 반응식
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]

참가 물질

6

반응물 2

HCID 66111Trimethylsilylacetylene2회HCID 681818044-(6-Bromo-2-ethoxy-1,3-benzodiazol-1-yl)pyrimidin-2-amine

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매2회HCID 178418397HCID 178418397, 화합물촉매2회HCID 8082Piperidine용매

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온도
65 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-236d2508d5f1491e9d73a51f28cb33d2
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901313B2

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