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

HRID 1945704ノート

反応式

HRID 1945704 の反応式
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+]>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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
130 °C

実験手順

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)

後処理

  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)

出典と根拠

ORDレコード
ord-ff7fbc25ce864c84832932dfd8a27138
出典データセット
uspto-grants-2013_03
特許番号
US08394796B2

反応ノート

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