Tetrahydrofuran → (4-(1-(3-Amino-1-cyclopentyl-3-oxopropyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

HRID 334193

反応式

HRID 334193 の反応式
[C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][N:21](/[C:23](/[CH:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)=[CH:24]\[C:25]([NH2:27])=[O:26])[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].O1CCCC1.[H][H]>[Pd]>[C:1]([O:7][CH2:8][N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([C:18]3[CH:19]=[N:20][N:21]([CH:23]([CH:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)[CH2:24][C:25]([NH2:27])=[O:26])[CH:22]=3)[C:12]=2[CH:11]=[CH:10]1)(=[O:6])[C:2]([CH3:4])([CH3:5])[CH3:3]

参加物

5

反応物 3

HCID 8028TetrahydrofuranHCID 59420169(Z)-(4-(1-(3-Amino-1-cyclopentyl-3-oxoprop-1-enyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalateHCID 178418361HCID 178418361、化合物2 回

生成物 1

HCID 59420164(4-(1-(3-Amino-1-cyclopentyl-3-oxopropyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate収率 99.7%

試薬・触媒・溶媒 1

HCID 23938Palladium触媒

実験手順

To a 25 ml round bottom flask equipped with a stir bar was charged (Z)-(4-(1-(3-amino-1-cyclopentyl-3-oxoprop-1-enyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (10, 1.15 g, 2.63 mmol), tetrahydrofuran (THF, 20.0 ml, 246 mmol) and 10% palladium on carbon (50% wet, 130 mg) at room temperature. The resulting reaction mixture was degassed three times back filling with hydrogen gas each time before the hydrogenation reaction was conducted under a steady stream of hydrogen gas released by a hydrogen balloon. The reaction was checked after 17 h and was found to be complete. The reaction mixture was then filtered through a Celite bed to remove the catalyst and the Celite bed was rinsed with a small volume of tetrahydrofuran (THF). The combined filtrates were concentrated under reduced pressure to afford the crude (4-(1-(3-amino-1-cyclopentyl-3-oxopropyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (11, 1.15 g, 1.153 g theoretical, 99% yield) as a yellow to brown oil, which solidified upon standing in vacuum at room temperature. This crude product (11) was found to be pure enough (>98% by HPLC) to do the following reaction without further purification. For 11: 1H NMR (DMSO-d6, 300 MHz) δ ppm 8.73 (s, 1H), 8.60 (s, 1H), 8.27 (s, 1H), 7.70 (d, 1H, J=3.8 Hz), 7.32 (bs, 1H), 7.09 (d, 1H, J=3.8 Hz), 6.75 (bs, 1H), 6.21 (s, 2H), 4.56 (td, 1H, J=4.0, 9.8 Hz), 2.86 (dd, 1H, J=10.5, 5.6 Hz), 2.63 (dd, 1H, J=4.0, 15.3 Hz), 2.32 (m, 1H), 1.77 (m, 1H), 1.56-1.19 (m, 7H), 1.06 (s, 9H); LCMS (EI) m/e 439 (M++H); C23H30N6O3 (MW, 438.52), LCMS (EI) m/e 439 (M++H).

後処理

  1. customTo a 25 ml round bottom flask equipped with a stir bar
  2. customThe resulting reaction mixture
  3. customwas degassed three times
  4. custombefore the hydrogenation reaction
  5. filtrationThe reaction mixture was then filtered through a Celite bed
  6. customto remove the catalyst
  7. washthe Celite bed was rinsed with a small volume of tetrahydrofuran (THF)
  8. concentrationThe combined filtrates were concentrated under reduced pressure

出典と根拠

ORDレコード
ord-9be59427a3c845f194f840bc7bd1576f
出典データセット
uspto-grants-2014_11
特許番号
US08883806B2

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