Trifluoroacetic acid → 3-morpholino-7-(pyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

HRID 335934ノート

反応式

HRID 335934 の反応式
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]3[C:20]4([CH2:24][S:23][C:22]([N:25](COCC[Si](C)(C)C)COCC[Si](C)(C)C)=[N:21]4)[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([C:42]5[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=5)[CH:18]=4)[O:13][C:10]3=[N:11][CH:12]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[CH:8]=[C:9]3[C:20]4([CH2:24][S:23][C:22]([NH2:25])=[N:21]4)[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([C:42]5[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=5)[CH:18]=4)[O:13][C:10]3=[N:11][CH:12]=2)[CH2:5][CH2:6]1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 674368683-morpholino-7-(pyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

生成物 1

HCID 584662923-morpholino-7-(pyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
50 °C

実験手順

A solution of 3-morpholino-7-(pyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (0.066 g, 0.095 mmol) in 5 mL of DCM was treated with TFA (0.5 ml, 6.49 mmol). The reaction was stirred for 3 hrs at 50° C. The mixture was cooled to RT and was diluted with DCM (25 mL). The derived solution was washed with saturated sodium bicarbonate (50 mL). The aqueous layer was extracted with DCM (3×15 mL) and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified by column chromatography (RediSep 12 g, gradient elution 0-100% DCM: 100:10:1 DCM, MeOH, NH4OH) to provide 3-morpholino-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine as a racemic mixture. Chiral separation provided (S)-3-morpholino-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine and (R)-3-morpholino-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine, both isomers as a white solid. MS m/z=432.3.

後処理

  1. temperatureThe mixture was cooled to RT
  2. washThe derived solution was washed with saturated sodium bicarbonate (50 mL)
  3. extractionThe aqueous layer was extracted with DCM (3×15 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified by column chromatography (RediSep 12 g, gradient elution 0-100% DCM: 100:10:1 DCM, MeOH, NH4OH)

出典と根拠

ORDレコード
ord-ea8dd8c9eb604abc91daff745684cb91
出典データセット
uspto-grants-2014_11
特許番号
US08883782B2

反応ノート

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