Diisopropylethylamine → 4-{3-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-2-(1-ethyl-propyl)-6-methoxy-pyridine

HRID 245100노트

반응식

HRID 245100 반응식
[CH2:1]([CH:3]([C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=1)[C:9]([OH:11])=O)[CH2:4][CH3:5])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:48][C:49]1([CH3:69])[O:53][C@H:52]([CH2:54][O:55][C:56]2[C:65]([CH3:66])=[CH:64][C:59]([C:60]([NH:62]O)=[NH:61])=[CH:58][C:57]=2[CH2:67][CH3:68])[CH2:51][O:50]1>C1COCC1.CN(C=O)C.CC(=O)OCC>[CH3:48][C:49]1([CH3:69])[O:53][C@H:52]([CH2:54][O:55][C:56]2[C:65]([CH3:66])=[CH:64][C:59]([C:60]3[N:62]=[C:9]([C:8]4[CH:12]=[C:13]([O:15][CH3:16])[N:14]=[C:6]([CH:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[CH:7]=4)[O:11][N:61]=3)=[CH:58][C:57]=2[CH2:67][CH3:68])[CH2:51][O:50]1

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584181082-(1-Ethylpropyl)-6-methoxyisonicotinic acidHCID 178436628HCID 178436628, 화합물

생성물 1

HCID 674914894-{3-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-2-(1-ethyl-propyl)-6-methoxy-pyridine수율 70.6%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid (190 mg, 732 μmol) in THF (10 mL) and DMF (2 mL), DIPEA (190 mg, 1.46 mmol) followed by TBTU (235 mg, 732 μmol) is added. The mixture is stirred at rt for 10 min before (R)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-N-hydroxy-5-methyl-benzamidine 226 mg, 732 μmol) is added. The mixture is stirred at rt for 1 h before it is diluted with EA and washed with water. The org. phase is separated and concentrated. The remaining residue is dissolved in dioxane (10 mL) and heated to 105° C. for 18 h. The mixture is cooled to rt, concentrated and the crude product is purified on prep. TLC plates using DCM containing 10% of methanol to give 4-{3-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-2-(1-ethyl-propyl)-6-methoxy-pyridine (256 mg) as a yellow oil; LC-MS: tR=1.28 min, [M+H]+=496.23.

후처리

  1. additionis added
  2. additionis added
  3. washwashed with water
  4. customphase is separated
  5. concentrationconcentrated
  6. dissolutionThe remaining residue is dissolved in dioxane (10 mL)
  7. temperatureheated to 105° C. for 18 h
  8. temperatureThe mixture is cooled to rt
  9. concentrationconcentrated
  10. customthe crude product is purified on prep

출처 및 근거

ORD 기록
ord-e039f9faf6f3481d908c4bff18a47a82
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658675B2

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