Morpholine → 3-iodo-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 898021ノート

反応式

HRID 898021 の反応式
Br[CH2:2][CH2:3][CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[N:12][C:13]([NH2:14])=[C:8]2[C:7]([I:15])=[N:6]1.[NH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C(N(CC)CC)C>CN(C)C=O>[I:15][C:7]1[C:8]2[C:9](=[N:10][CH:11]=[N:12][C:13]=2[NH2:14])[N:5]([CH2:4][CH2:3][CH2:2][N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[N:6]=1

参加物

5

反応物 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 223466991-(3-bromopropyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

生成物 1

HCID 223473583-iodo-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine収率 48%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

A suspension of 1-(3-bromopropyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.500 g, 1.31 mmol) in dimethylformamide (10 mL) was treated with morpholine (0.137 g, 1.572 mmol) and triethylamine (0.133 g, 1.31 mmol). The reaction mixture was stirred at 70° C. for 66.25 h. Solvent was removed under reduced pressure. Dichloromethane (15 mL) and 1 N hydrochloric acid (20 mL) were added. The layers were partitioned and the aqueous layer was washed with dichloromethane (100 mL). The aqueous layer was neutralized to pH 14 and then extracted with dichloromethane (250 mL). The organic layer was dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a step-wise gradient of 10% methanol in dichloromethane to 50% methanol in dichloromethane over 58 minutes on a 35 g ISCO column. The column afforded 0.244 g (48%) of pure 3-iodo-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine. 1H NMR (DMSO-d6, 400 MHz) δ 8.194 (s, 1H), 4.327-4.293 (t, 2H), 3.485-3.364 (m, 4H), 2.253-2.238 (m, 6H), 1.963-1.895 (m, 2H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 μm particle size, 33×4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt 0.71 min (100%), MH+ 389.0.

後処理

  1. customSolvent was removed under reduced pressure
  2. additionDichloromethane (15 mL) and 1 N hydrochloric acid (20 mL) were added
  3. customThe layers were partitioned
  4. washthe aqueous layer was washed with dichloromethane (100 mL)
  5. extractionextracted with dichloromethane (250 mL)
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude material was purified by flash chromatography on silica gel using a step-wise gradient of 10% methanol in dichloromethane to 50% methanol in dichloromethane over 58 minutes on a 35 g ISCO column

出典と根拠

ORDレコード
ord-4eccd4cf4844474486abad53906d7e4b
出典データセット
uspto-grants-2005_07
特許番号
US06921763B2

反応ノート

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