Pyridine → 5-[(4aR,7aR)-2-Amino-6-[5-fluoro-4-(2-hydroxypropan-2-yl)pyrimidin-2-yl]-4a,5,6,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a(4H)-yl]thiophene-2-carbonitrile

HRID 338159ノート

反応式

HRID 338159 の反応式
[C:1]([C:3]1[S:7][C:6]([C@:8]23[CH2:16][N:15]([C:17]4[N:22]=[C:21]([C:23]([OH:26])([CH3:25])[CH3:24])[C:20]([F:27])=[CH:19][N:18]=4)[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:28]C(=O)C2C=CC=CC=2)=[N:9]3)=[CH:5][CH:4]=1)#[N:2].N1C=CC=CC=1.Cl.CON>C(O)C>[NH2:28][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:14][N:15]([C:17]3[N:22]=[C:21]([C:23]([OH:26])([CH3:25])[CH3:24])[C:20]([F:27])=[CH:19][N:18]=3)[CH2:16][C@:8]2([C:6]2[S:7][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[N:9]=1

参加物

5

反応物 3

HCID 1049PyridineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 86762238N-{(4aR,7aR)-7a-(5-Cyanothiophen-2-yl)-6-[5-fluoro-4-(2-hydroxypropan-2-yl)pyrimidin-2-yl]-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl}benzamide

生成物 1

HCID 867622495-[(4aR,7aR)-2-Amino-6-[5-fluoro-4-(2-hydroxypropan-2-yl)pyrimidin-2-yl]-4a,5,6,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a(4H)-yl]thiophene-2-carbonitrile収率 90%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
55 °C

実験手順

To a stirred solution of N-{(4aR,7aR)-7a-(5-cyanothiophen-2-yl)-6-[5-fluoro-4-(2-hydroxypropan-2-yl)pyrimidin-2-yl]-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl}benzamide (364 mg, 0.697 mmol) in ethanol (14 mL) is added pyridine (563 μL, 6.96 mmol) and O-methylhydroxylamine hydrochloride (582 mg, 6.96 mmol). The solution is heated to 55° C. under an atmosphere of nitrogen for 21 hours. The resulting solution is allowed to cool for a few minutes then concentrated under reduced pressure. Dichloromethane (30 mL) is added and again the solution is concentrated under reduced pressure. The residue is diluted with ethyl acetate (50 mL), water (25 mL), and saturated aqueous sodium bicarbonate (10 mL). The phases are separated and the ethyl acetate phase is dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography, eluting with dichloromethane/ethyl acetate, 70:30 for 20 minutes, and then a gradient to 0:100 to give the title compound (261 mg, 90%) as a white foam. MS/ES (m/z) 419.0 (M+H).

後処理

  1. temperatureto cool for a few minutes
  2. concentrationthen concentrated under reduced pressure
  3. additionDichloromethane (30 mL) is added
  4. concentrationagain the solution is concentrated under reduced pressure
  5. additionThe residue is diluted with ethyl acetate (50 mL), water (25 mL), and saturated aqueous sodium bicarbonate (10 mL)
  6. customThe phases are separated
  7. dry with materialthe ethyl acetate phase is dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by silica gel chromatography
  11. washeluting with dichloromethane/ethyl acetate, 70:30 for 20 minutes

出典と根拠

ORDレコード
ord-6cd358322d38416ba38cfeeae3ef59f9
出典データセット
uspto-grants-2014_11
特許番号
US08889856B2

反応ノート

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