Triethylamine → (4-{4-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-phenyl}-cyclohexyl)-acetic acid ethyl ester

HRID 631936노트

반응식

HRID 631936 반응식
[CH2:1]([O:3][C:4]([CH2:6][CH:7]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:23]=[N:22][N:21]([CH3:24])[C:20]=3C(O)=O)=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)=[O:5])[CH3:2].C([N:30]([CH2:33]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:42])C=CC=CC=1.[C:52]1([C@H:58]([OH:60])[CH3:59])[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:5])[CH2:6][CH:7]1[CH2:8][CH2:9][CH:10]([C:13]2[CH:14]=[CH:15][C:16]([C:19]3[N:23]=[N:22][N:21]([CH3:24])[C:20]=3[NH:30][C:33]([O:60][C@@H:58]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[CH3:59])=[O:42])=[CH:17][CH:18]=2)[CH2:11][CH2:12]1)[CH3:2]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 6375161-Phenylethanol, (R)-HCID 715005385-[4-(4-ethoxycarbonylmethyl-cyclohexyl)-phenyl]-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid

생성물 1

HCID 118061991(4-{4-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-phenyl}-cyclohexyl)-acetic acid ethyl ester수율 35%

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
81 °C

실험 절차

To a light brown solution of 5-[4-(4-ethoxycarbonylmethyl-cyclohexyl)-phenyl]-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid (37 mg, 0.099 mmol) in toluene (5 mL) was added triethylamine (20.2 mg, 27.8 μL, 0.199 mmol) at room temperature. To the resulting solution was added diphenylphosphoryl azide (30.2 mg, 23.6 μL, 0.11 mmol) followed by (R)-1-phenylethanol (13.4 mg, 13.2 μL, 0.11 mmol) at room temperature. The resulting solution was heated with oil bath to 81° C. and stirred for 1 h at which time TLC analysis indicated the absence of the starting material. Then, the reaction mixture was cooled to room temperature and the solvent was removed under vacuum. The crude residue was treated with dichloromethane (10 mL) and filtered. The filtrate was loaded onto an ISCO (40 g) column chromatography eluting with ethyl acetate in hexanes (0-100%). The desired fractions were combined and the solvent was removed under vacuum to obtain (4-{4-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-phenyl}-cyclohexyl)-acetic acid ethyl ester (17 mg, 35% yield) as a white solid. LC/MS calcd for C28H34N4O4 (m/e) 490, obsd. 491.3 [M+H, ES+].

후처리

  1. temperatureThen, the reaction mixture was cooled to room temperature
  2. customthe solvent was removed under vacuum
  3. additionThe crude residue was treated with dichloromethane (10 mL)
  4. filtrationfiltered
  5. washeluting with ethyl acetate in hexanes (0-100%)
  6. customthe solvent was removed under vacuum

출처 및 근거

ORD 기록
ord-4c6b4f09cac04491b5ac7a258fa6c796
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321738B2

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