Iodoethane → tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate

HRID 1749046노트

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HRID 1749046 반응식
N12CCCN=C1CCC[CH2:3][CH2:2]2.[NH2:12][C:13]1[N:14]=[CH:15][C:16]([C:28]2[NH:32][N:31]=[C:30]([CH:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)[N:29]=2)=[N:17][C:18]=1[C:19]1[O:20][C:21]([C:24]([CH3:27])([CH3:26])[CH3:25])=[N:22][N:23]=1.ICC>O>[NH2:12][C:13]1[N:14]=[CH:15][C:16]([C:28]2[N:32]([CH2:2][CH3:3])[N:31]=[C:30]([CH:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)[N:29]=2)=[N:17][C:18]=1[C:19]1[O:20][C:21]([C:24]([CH3:26])([CH3:27])[CH3:25])=[N:22][N:23]=1

참가 물질

5

반응물 3

HCID 6340Iodoethane2회HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2회HCID 178451827HCID 178451827, 화합물

생성물 1

HCID 86727667tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate수율 73%

시약·촉매·용매 1

HCID 962Water용매

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온도
35 °C

실험 절차

1,8-Diazabicyclo[5.4.0]undec-7-ene (76 mL, 511.14 mmol) was added to a suspension of tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate (150 g, 319.46 mmol) in 2-methylTHF (1.2 L). Iodoethane (46 mL, 575.03 mmol) was added and the mixture was stirred for 16 hours at 35° C. Further iodoethane (46 mL, 575.03 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (76 mL, 511.14 mmol) were added and stirring was continued for 24 hours at 35° C. The mixture was poured into water and the insoluble material was isolated by filtration, washed with water and MTBE and dried in vacuo to afford tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate (116 g, 73.0%) as a yellow solid. The filtrate was extracted with DCM and the organic solution was dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica using gradient elution (30% MTBE/heptane to 100% MTBE). A second crop of the desired product (12 g, 24.12 mmol, 7.55%), was thus isolated as a yellow solid which was later combined with the first crop: 1H NMR Spectrum: (DMSO-d6) 1.41 (9H, s), 1.44 (9H, s), 1.48 (3H, t), 1.52-1.69 (2H, m), 1.87-2.04 (2H, n), 2.79-3.03 (3H, m) 3.86-4.03 (2H, m, 4.59 (2H, q), 7.89 (2H, s), 8.85 (1H, s); Mass Spectrum [M+H]+=498.

후처리

  1. stirringstirring
  2. waitwas continued for 24 hours at 35° C
  3. customthe insoluble material was isolated by filtration
  4. washwashed with water and MTBE
  5. customdried in vacuo

출처 및 근거

ORD 기록
ord-f29bc110541e45f892a02280ca167626
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09155727B2

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