Acetic Acid → N-Methyl-N-[(3R,4R)-4-methyl-3-piperidinyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 1517984ノート

反応式

HRID 1517984 の反応式
O.C([N:9]1[CH2:14][CH2:13][CH:12]([CH3:15])[CH:11]([N:16]([CH3:26])[C:17]2[C:18]3[CH:25]=[CH:24][NH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:10]1)C1C=CC=CC=1.C(O)(=O)C>[OH-].[OH-].[Pd+2].C(O)(C)C>[CH3:26][N:16]([C@@H:11]1[C@H:12]([CH3:15])[CH2:13][CH2:14][NH:9][CH2:10]1)[C:17]1[C:18]2[CH:25]=[CH:24][NH:23][C:19]=2[N:20]=[CH:21][N:22]=1

参加物

6

反応物 3

HCID 176Acetic AcidHCID 962WaterHCID 12084829N-(1-Benzyl-4-methylpiperidin-3-yl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

生成物 1

HCID 23401507N-Methyl-N-[(3R,4R)-4-methyl-3-piperidinyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

試薬・触媒・溶媒 2

HCID 9942167Palladium hydroxide触媒HCID 3776Isopropanol溶媒

反応条件

温度
50 °C

実験手順

To a clean, dry, nitrogen-purged 2 L hydrogenation reactor were charged 20 wt % Pd(OH)2/C (24.0 g, 50% water wet), water (160 ml), isopropanol (640 ml), (1-benzyl-4-methyl-piperidin-3-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (160.0 g, 0.48 mol), and acetic acid (28.65 g, 0.48 mol). The reactor was purged with three times at 50 psi with nitrogen and three times at 50 psi with hydrogen. Once purging was complete, the reactor was heated to 45-55° C. and pressurized to 50 psi with hydrogen through a continuous feed. The hydrogen uptake was monitored until no hydrogen was consumed for 1 hour. The reactor was cooled to 20-30° C. and purged three times at 50 psi with nitrogen. The reaction mixture was filtered through wet Celite and the filtrate was sent to a clean, dry, nitrogen-purged vessel. A solution of sodium hydroxide (39.33 g) in water (290 ml) was charged and the mixture was stirred for a minimum of 1 hour then heated to 75-90° C. The isopropanol was removed by distillation. The reaction mixture was cooled to 20-30° C. and 2-methyltetrahydrofuran (1.6 L) was added. The aqueous layer was drained off and the 2-methyltetrahydrofuran was displaced with toluene (1.6 L). The distillation was continued until the final volume was 800 ml. The slurry was cooled to 20-30° C. and held for a minimum of 7 hours. The resulting solids were isolated by filtration and washed with toluene (480 ml). After drying under vacuum between 40-50° C. for a minimum of 24 hours with a slight nitrogen bleed 102.3 g (87.3%) of the title compound were isolated.

後処理

  1. customTo a clean, dry
  2. customnitrogen-purged 2 L hydrogenation reactor
  3. customThe reactor was purged with three times at 50 psi with nitrogen and three times at 50 psi with hydrogen
  4. customOnce purging
  5. customwas consumed for 1 hour
  6. temperatureThe reactor was cooled to 20-30° C.
  7. custompurged three times at 50 psi with nitrogen
  8. filtrationThe reaction mixture was filtered through wet Celite
  9. customdry
  10. customnitrogen-purged vessel
  11. additionA solution of sodium hydroxide (39.33 g) in water (290 ml) was charged
  12. temperaturethen heated to 75-90° C
  13. customThe isopropanol was removed by distillation
  14. temperatureThe reaction mixture was cooled to 20-30° C.
  15. addition2-methyltetrahydrofuran (1.6 L) was added
  16. distillationThe distillation
  17. temperatureThe slurry was cooled to 20-30° C.
  18. customheld for a minimum of 7 hours
  19. customThe resulting solids were isolated by filtration
  20. washwashed with toluene (480 ml)
  21. customAfter drying under vacuum between 40-50° C. for a minimum of 24 hours with a slight nitrogen
  22. customwere isolated

出典と根拠

ORDレコード
ord-a65a877e56c64861a68000e6fab9a519
出典データセット
uspto-grants-2012_07
特許番号
US08232394B2

反応ノート

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