Potassium Carbonate → tert-butyl-4-(5-{4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 1530560노트

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HRID 1530560 반응식
[CH3:1][CH:2]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[N:21]([CH:22]=2)[CH2:20][CH2:19][O:18][C:17]2[C:12]3=[CH:13][CH:14]=[C:15]([C:23]3[NH:27][N:26]=[CH:25][CH:24]=3)[CH:16]=2)=[N:7][CH:6]=[N:5]1)[CH3:3].CS(O[CH:33]1[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]1)(=O)=O.C([O-])([O-])=O.[K+].[K+]>CC#N>[C:42]([O:41][C:39]([N:36]1[CH2:37][CH2:38][CH:33]([N:27]2[C:23]([C:15]3[CH:16]=[C:17]4[C:12](=[CH:13][CH:14]=3)[C:11]3[N:21]([CH:22]=[C:9]([C:8]5[N:4]([CH:2]([CH3:1])[CH3:3])[N:5]=[CH:6][N:7]=5)[N:10]=3)[CH2:20][CH2:19][O:18]4)=[CH:24][CH:25]=[N:26]2)[CH2:34][CH2:35]1)=[O:40])([CH3:45])([CH3:43])[CH3:44]

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidineHCID 683130694-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-12-(1H-pyrazol-5-yl)-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene

생성물 1

HCID 68313074tert-butyl-4-(5-{4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate수율 7%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

A mixture of 4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-12-(1H-pyrazol-5-yl)-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (1.00 g, 2.77 mmol), tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (1.95 g, 6.92 mmol), and K2CO3 (1.90 g, 13.8 mmol) in CH3CN (50.0 mL) was stirred at 100° C. for 60 hr. After removal of the solvents, the residue was treated with water and extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over MgSO4, filtered, and evaporated to afford the crude product, which was purified by reverse phase combiflash eluting with 0-50% gradient CH3CN in 0.5% NH4HCO3 and followed by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to give tert-butyl-4-(5-{4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate (100 mg, 7% yield) as pale yellow solid. LCMS (ESI) m/z: 545.3 [M+H+]. 1H-NMR (500 MHz, DMSO-d6): δ 8.54 (d, J=10.5 Hz, 1H), 7.99 (s, 1H), 7.93 (s, 1H), 7.56 (s, 1H), 7.26, (dd, J=2.5 Hz, 10.5 Hz, 1H), 7.12 (s, 1H), 6.40 (s, 1H), 5.94-5.91 (m, 1H), 4.59-4.56 (m, 4H), 4.42 (s, 1H), 4.02-3.99 (m, 2H), 2.84-2.83 (m, 2H), 1.92-1.85 (m, 4H), 1.50 (s, 6H), 1.40 (s, 9H).

후처리

  1. customAfter removal of the solvents
  2. additionthe residue was treated with water
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto afford the crude product, which
  9. customwas purified by reverse phase combiflash
  10. washeluting with 0-50% gradient CH3CN in 0.5% NH4HCO3
  11. customfollowed by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

출처 및 근거

ORD 기록
ord-74aee4b9bb6c46d5bdb616ad122bd3c3
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090628B2

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