Sodium Carbonate → (S)-2-fluoro-4-(2-(2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)-methyl)morpholino)pyrimidin-5-yl)benzaldehyde

HRID 1478587노트

반응식

HRID 1478587 반응식
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][N:15]3[C:19]4=[N:20][C:21]([C:24]5[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=5)=[CH:22][N:23]=[C:18]4[N:17]=[N:16]3)[CH2:9]2)=[N:6][CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].[F:36][C:37]1[CH:44]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH:42]=[CH:41][C:38]=1[CH:39]=[O:40]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[F:36][C:37]1[CH:44]=[C:43]([C:2]2[CH:3]=[N:4][C:5]([N:8]3[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][N:15]4[C:19]5=[N:20][C:21]([C:24]6[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=6)=[CH:22][N:23]=[C:18]5[N:17]=[N:16]4)[CH2:9]3)=[N:6][CH:7]=2)[CH:42]=[CH:41][C:38]=1[CH:39]=[O:40]

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 532171132-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehydeHCID 73507291HCID 73507291, 화합물

생성물 1

HCID 118364829(S)-2-fluoro-4-(2-(2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)-methyl)morpholino)pyrimidin-5-yl)benzaldehyde수율 79.1%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

In a pressure tube reactor, (S)-4-(5-bromopyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine (50 mg, 0.11 mmol) was added, and then 1M Na2CO3 (0.33 mL, 0.33 mmol) was added. Pd(PPh3)4 (6 mg, 0.005 mmol) was further added, and then 1,4-dioxane (1 mL) and 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)benzaldehyde (41 mg, 0.16 mmol) were added. The mixture was stirred at room temperature for 10 minutes under nitrogen gas, and then stirred at 105° C. for 13 hours. When the reaction was completed, the organic layer was extracted with ethyl acetate and water, and the extra water was removed by sodium sulfate, followed by concentration under reduced pressure. Solid was generated using ether and hexane, followed by filtration, to give (S)-2-fluoro-4-(2-(2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)-methyl)morpholino)pyrimidin-5-yl)benzaldehyde (41 mg, 0.087 mmol) with a yield of 76%.

후처리

  1. stirringstirred at 105° C. for 13 hours
  2. extractionthe organic layer was extracted with ethyl acetate and water
  3. customthe extra water was removed by sodium sulfate
  4. concentrationfollowed by concentration under reduced pressure
  5. filtrationfollowed by filtration

출처 및 근거

ORD 기록
ord-24e19e81349d497caca9b7fcc908669e
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09403831B2

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