Hydrochloric Acid → imino-methyl-[1-[6-[(3R)-3-methylmorpholin-4-yl]-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl]cyclopropyl]-oxo-lambda6-sulfane

HRID 888990ノート

反応式

HRID 888990 の反応式
[OH-].[Na+].[CH3:3][C@@H:4]1[CH2:9][O:8][CH2:7][CH2:6][N:5]1[C:10]1[CH:15]=[C:14]([C:16]2([S:19]([CH3:22])(=[NH:21])=[O:20])[CH2:18][CH2:17]2)[N:13]=[C:12]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]3[N:29](S(C4C=CC(C)=CC=4)(=O)=O)[CH:30]=[CH:31][C:24]=23)[N:11]=1.O.Cl>COCCOC>[CH3:3][C@@H:4]1[CH2:9][O:8][CH2:7][CH2:6][N:5]1[C:10]1[CH:15]=[C:14]([C:16]2([S:19]([CH3:22])(=[NH:21])=[O:20])[CH2:18][CH2:17]2)[N:13]=[C:12]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]3[NH:29][CH:30]=[CH:31][C:24]=23)[N:11]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium Hydroxide2 回HCID 86660216(3R)-3-methyl-4-(6-(1-(S-methylsulfonimidoyl)cyclopropyl)-2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)morpholine

生成物 1

HCID 86660217imino-methyl-[1-[6-[(3R)-3-methylmorpholin-4-yl]-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl]cyclopropyl]-oxo-lambda6-sulfane収率 52%

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
50 °C

実験手順

Sodium hydroxide, 2M aqueous solution (9.95 ml, 19.90 mmol) was added to (3R)-3-methyl-4-(6-(1-(S-methylsulfonimidoyl)cyclopropyl)-2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)morpholine (6.44 g, 11.37 mmol) in DME (100 ml)/water (25.00 ml). The resulting solution was stirred at 50° C. for 18 hours. Further NaOH, 2M aqueous solution (18 ml, 36.00 mmol) was added and the mixture was stirred at 50° C. for a further 3 days. The reaction mixture was acidified with 2M HCl (˜22 ml) to pH5. The reaction mixture was evaporated and the residue was dissolved in DCM (250 ml) and washed with water (200 ml). The organic layer was dried over MgSO4, filtered and then evaporated to approximately 50 ml in volume. The solution was purified by flash chromatography on silica, eluting with a gradient of 0 to 7% MeOH in DCM. Pure fractions were evaporated to afford 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-(S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (2.440 g, 52%); 1H NMR (400 MHz, DMSO-d6) 1.27 (3H, d), 1.42 (1H, dd), 1.47-1.58 (2H, m), 1.68-1.80 (1H, m), 3.10 (3H, s), 3.24-3.31 (1H, m), 3.51 (1H, t), 3.66 (1H, dd), 3.80 (1H, d), 3.83-3.88 (1H, m), 4.00 (1H, dd), 4.20 (1H, s), 4.57 (1H, s), 6.99 (1H, d), 7.22 (1H, dd), 7.53-7.63 (1H, m), 7.94 (1H, d), 8.34 (1H, t), 11.80 (1H, s); m/z: (ES+) MH+, 413.47.

後処理

  1. stirringthe mixture was stirred at 50° C. for a further 3 days
  2. customThe reaction mixture was evaporated
  3. dissolutionthe residue was dissolved in DCM (250 ml)
  4. washwashed with water (200 ml)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated to approximately 50 ml in volume
  8. customThe solution was purified by flash chromatography on silica
  9. washeluting with a gradient of 0 to 7% MeOH in DCM
  10. customPure fractions were evaporated

出典と根拠

ORDレコード
ord-c6e45f06839d422ba25f08eb0fd228c3
出典データセット
uspto-grants-2012_08
特許番号
US08252802B2

反応ノート

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