2,2,6,6-Tetramethylpiperidine → HCID 86706147, 화합물

HRID 2176298노트

반응식

HRID 2176298 반응식
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:27])[C@@H:24]([NH2:26])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[C:28]([CH:31]([O:36][C:37](=[O:43])[C:38]([CH3:42])([CH3:41])[CH:39]=[CH2:40])[CH:32]1[CH2:35][O:34][CH2:33]1)(O)=[O:29].CC1(C)CCCC(C)(C)N1.F[P-](F)(F)(F)(F)F.C(C(=NO[C+](N(C)C)N1CCOCC1)C(OCC)=O)#N>CN(C)C=O.ClCCl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:27])[C@@H:24]([NH:26][C:28]([CH:31]([O:36][C:37](=[O:43])[C:38]([CH3:42])([CH3:41])[CH:39]=[CH2:40])[CH:32]4[CH2:35][O:34][CH2:33]4)=[O:29])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 86706144HCID 86706144, 화합물HCID 86706146HCID 86706146, 화합물HCID 178472143HCID 178472143, 화합물

생성물 1

HCID 86706147HCID 86706147, 화합물수율 42%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

A stirred solution of (S)-1-((S)-2-amino-propionyl)-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (141 mg, 0.618 mmol) and 2,2-dimethyl-but-3-enoic acid carboxy-oxetan-3-yl-methyl ester (315 mg, 0.725 mmol) in anhydrous N,N-dimethylformamide (10 mL) was cooled to 0° C. under nitrogen. 2,2,6,6-Tetramethylpiperidine (261 mg, 313 μL, 1.85 mmol) was added, rapidly followed by (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (371 mg, 0.865 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 15 h. The reaction mixture was diluted with dichloromethane and washed with saturated ammonium chloride solution (2×), saturated sodium bicarbonate solution (2×), the organic layer was filtered through a phase-separator and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:0 to 0:1 to give the title compound (167 mg, 42%) as a yellow/brown foam and as an approximate 1:1 mixture of diastereoisomers. LCMS (m/z) 644.2, 646.1[M+H], Tr=2.63 min.

후처리

  1. washwashed with saturated ammonium chloride solution (2×), saturated sodium bicarbonate solution (2×)
  2. filtrationthe organic layer was filtered through a phase-separator
  3. customevaporated
  4. customThe residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-ade14bc13d72466c9b37879833c51c9c
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09062092B2

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