Sodium t-butoxide → 4-[4-(2-Methyl-6-[1,2,4]triazol-1-yl-pyridin-3-ylamino)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931617

반응식

HRID 1931617 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22](Cl)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][C:25]1[C:30]([NH2:31])=[CH:29][CH:28]=[C:27]([N:32]2[CH:36]=[N:35][CH:34]=[N:33]2)[N:26]=1.CC(C)([O-])C.[Na+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(CN1P2N(CC(C)C)CCN(CCN2CC(C)C)CC1)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([NH:31][C:30]4[C:25]([CH3:24])=[N:26][C:27]([N:32]5[CH:36]=[N:35][CH:34]=[N:33]5)=[CH:28][CH:29]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 3

HCID 23676156Sodium t-butoxideHCID 532992722-methyl-6-(1H-1,2,4-triazol-1-yl)pyridin-3-amine2회HCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2회

생성물 1

HCID 579649544-[4-(2-Methyl-6-[1,2,4]triazol-1-yl-pyridin-3-ylamino)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester수율 26%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane촉매HCID 6228Dimethylformamide용매

반응 조건

온도
160 °C

실험 절차

A mixture of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 50 mg, 0.15 mmol), 2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-ylamine (Intermediate 7, Step 2; 26 mg, 0.15 mmol), palladium(II) acetate (0.3 mg, 0.01 eq), triisobutylphosphatrane (1 mg, 0.02 eq) and sodium tert-butoxide (34 mg, 0.36 mmol) in dimethylformamide (2 mL) was heated in the microwave oven at 160° C. for 10 min. The mixture was filtered through a PTFE filter with a 0.45 μM pore size to remove the catalyst, and the solid was rinsed with ethyl acetate. Ethyl acetate and water were added to the combined filtrate and washings, and the aqueous layer was extracted twice with ethyl acetate. The ethyl acetate layers were combined, evaporated, and purified by preparative C18 HPLC, eluting with 10-100% acetonitrile/water. Samples containing the product were extracted twice with dichloromethane and the solvent was evaporated to give 4-[4-(2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-ylamino)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (18 mg, 26%) as a light yellow powder. 1H NMR (300 MHz, DMSO-d6) δ 1.43 (s, 9H), 1.75-2.07 (m, 4H), 2.99 (br s, 2H), 3.98-4.15 (m, 2H), 4.77-5.00 (m, 1H), 7.77 (d, 1H, J=8.5 Hz), 8.04-8.15 (m, 2H), 8.30 (s, 2H), 9.33 (s, 1H), 10.00 (br s, 1H). Mass spectrum (ES) MH+=477. HRMS Calcd. for C23H29N10O2 (MH+): 477.2470. Found: 477.2468.

후처리

  1. filtrationThe mixture was filtered through a PTFE
  2. filtrationfilter with a 0.45 μM pore size
  3. customto remove the catalyst
  4. washthe solid was rinsed with ethyl acetate
  5. additionEthyl acetate and water were added to the combined filtrate and washings
  6. extractionthe aqueous layer was extracted twice with ethyl acetate
  7. customevaporated
  8. custompurified by preparative C18 HPLC
  9. washeluting with 10-100% acetonitrile/water
  10. additionSamples containing the product
  11. extractionwere extracted twice with dichloromethane
  12. customthe solvent was evaporated

출처 및 근거

ORD 기록
ord-f844dfc021ba408c91e6406e241ddaa9
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

연결된 노트

불러오는 중…