4-Cyanopiperidine → 1-{2-[2-Amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-1,2,3,4-tetrahydroisoquinolin-7-yl}piperidine-4-carbonitrile

HRID 2090322

반응식

HRID 2090322 반응식
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.[NH:26]1[CH2:31][CH2:30][CH:29]([C:32]#[N:33])[CH2:28][CH2:27]1.CC(C)([O-])C.[Na+]>CC(O)=O.CC(P(C(C)(C)C)C1C(C2[C-]=CC=CC=2)=CC=CC=1)(C)C.[Pd]>[NH2:25][C:14]1[N:13]=[C:12]([N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][C:2]([N:26]4[CH2:31][CH2:30][CH:29]([C:32]#[N:33])[CH2:28][CH2:27]4)=[CH:3][CH:4]=3)[CH2:9]2)[CH:17]=[C:16]([N:18]2[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]2)[N:15]=1

참가 물질

5

반응물 3

HCID 1382234-CyanopiperidineHCID 23676156Sodium t-butoxideHCID 467010484-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine

생성물 1

HCID 467014621-{2-[2-Amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-1,2,3,4-tetrahydroisoquinolin-7-yl}piperidine-4-carbonitrile

시약·촉매·용매 1

HCID 119822622-(2'-Di-tert-butylphosphine)biphenylpalladium(II) acetate촉매

반응 조건

온도
120 °C

실험 절차

A mixture of 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (40 mg, 0.1 mmol), piperidine-4-carbonitrile (22 mg, 0.20 mmol, Oakwood, Cat. No. 024547), sodium tert-butoxide (23 mg, 0.24 mmol), 2-(2′-di-tert-butylphosphine)biphenyl palladium(II) acetate (2.8 mg, 0.0060 mmol, Aldrich, Cat. No. 655414) in 1,4-dioxane (1 mL) was degassed with nitrogen and then heated at 120° C. overnight. The reaction mixture was cooled to r.t. and concentrated under reduced pressure. The residue was dissolved in MeOH and purified by RP-HPLC (pH=10) to afford the desired compound. LCMS (M+H)+: m/z=433.3.

후처리

  1. custom655414) in 1,4-dioxane (1 mL) was degassed with nitrogen
  2. temperatureThe reaction mixture was cooled to r.t.
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in MeOH
  5. custompurified by RP-HPLC (pH=10)

출처 및 근거

ORD 기록
ord-7d41bb556b24467fb5db54ab3a41d640
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08436008B2

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