Sodium Carbonate → 1-((2-(7-Chloroquinolin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-n,n-dimethylpiperidin-4-amine

HRID 1922876노트

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HRID 1922876 반응식
Cl[C:2]1[N:3]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.[Cl:27][C:28]1[CH:37]=[C:36]2[C:31]([C:32](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:34]=[N:35]2)=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[Cl:27][C:28]1[CH:37]=[C:36]2[C:31]([C:32]([C:2]3[N:3]=[C:4]([N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[C:5]4[S:10][C:9]([CH2:11][N:12]5[CH2:13][CH2:14][CH:15]([N:18]([CH3:19])[CH3:20])[CH2:16][CH2:17]5)=[CH:8][C:6]=4[N:7]=3)=[CH:33][CH:34]=[N:35]2)=[CH:30][CH:29]=1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 162180767-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolineHCID 575067401-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

생성물 1

HCID 498340421-((2-(7-Chloroquinolin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-n,n-dimethylpiperidin-4-amine수율 43%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 6342Acetonitrile용매

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온도
130 °C

실험 절차

A sealable tube was charged with [1-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-dimethyl-amine (0.150 g, 0.380 mmol), 7-chloroquinoline-4-boronic acid pinacol ester (0.132 g, 0.456 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.013 g, 0.02 mmol), 1 N aqueous sodium carbonate solution (1 mL) and acetonitrile (3 mL). The vessel was evacuated and back-filled with argon three times then sealed and heated at 130° C. for 90 min. The reaction mixture was cooled, concentrated, redissolved in ethyl acetate and filtered through celite. The filtrates were concentrated then purified by chromatography (silica, 10 to 20% methanol in dichloromethane) to give 104 (0.085 g, 43%) as a yellow solid. MS m/e 531 [M+H]+; 1H NMR (300 MHz, METHANOL-d4) δ ppm 1.48-1.67 (m, 2 H) 1.82-1.96 (m, 2 H) 2.07-2.26 (m, 3 H) 2.30 (s, 6 H) 3.07 (d, J=11.7 Hz, 2 H) 3.82-3.91 (m, 6 H) 4.02-4.11 (m, 4 H) 7.36 (s, 1 H) 7.60 (dd, J=9.1, 2.3 Hz, 1 H) 7.95 (d, J=4.5 Hz, 1 H) 8.10 (d, J=2.3 Hz, 1 H) 8.67 (d, J=9.4 Hz, 1 H) 8.98 (d, J=4.9 Hz, 1 H)

후처리

  1. customThe vessel was evacuated
  2. additionback-filled with argon three times
  3. customthen sealed
  4. temperatureThe reaction mixture was cooled
  5. concentrationconcentrated
  6. dissolutionredissolved in ethyl acetate
  7. filtrationfiltered through celite
  8. concentrationThe filtrates were concentrated
  9. customthen purified by chromatography (silica, 10 to 20% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-4905468efff6410bb7e2f5ac74ffee49
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173650B2

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