Triethylamine → HCID 66934449, 화합물

HRID 1366312노트

반응식

HRID 1366312 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13]SC3C([N+]([O-])=O)=CC=CN=3)[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([O:32]C(C)(C)C)=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl[CH2:59][C:60]([C:62]1[CH:63]=[CH:64][C:65]2[O:69][CH2:68][CH2:67][C:66]=2[CH:70]=1)=[O:61].CCN(CC)CC>CC(C)=O.O>[O:69]1[C:65]2[CH:64]=[CH:63][C:62]([C:60](=[O:61])[CH2:59][S:13][C@H:10]3[C:11](=[O:12])[N:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[C@@H:9]3[C:24]3[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([OH:32])=[O:31])=[CH:37][CH:38]=3)=[CH:70][C:66]=2[CH2:67][CH2:68]1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 11776Triphenylphosphine2회HCID 65041702-Chloro-1-(2,3-dihydrobenzofuran-5-yl)ethanone2회HCID 86639220{4-[(2R,3R)-1-(4-fluoro-phenyl)-3-(3-nitro-pyridin-2-yldisulfanyl)-4-oxo-azetidin-2-yl]-phenoxy}-acetic acid tert-butyl ester

생성물 1

HCID 66934449HCID 66934449, 화합물

시약·촉매·용매 2

HCID 180Acetone용매HCID 962Water용매

실험 절차

To a stirred solution of tert-butyl (4-{(2R,3R)-1-(4-fluorophenyl)-3-[(3-nitropyridin-2-yl)dithio]-4-oxoazetidin-2-yl}phenoxy)acetate (50.0 mg, 0.090 mmol) in acetone (6 ml) and water (0.8 ml) was added triphenylphosphine (33.3 mg, 0.013 mmol). The reaction mixture was stirred for 15 minutes. The solvent was removed under reduced pressure and the crude thiol was dissolved in DCM (12 ml). Et3N, (30 pd, 0.22 mmol) was added. After 5 minutes, 2-chloro-1-(2,3-dihydro-1-benzofuran-5-yl)ethanone (37.2 mg, 0.19 mmol) was added and the reaction mixture was stirred overnight. Additional triphenylphosphine (11.6 mg, 0.04 mmol), Et3N (10 μl, 1, 0.07 mmol) and 2-chloro-1-(2,3-dihydro-1-benzofuran-5-yl)ethanone (7.2 mg, 0.04 mmol) were added and the reaction mixture was stirred for 1 hour. The formation of the tert-butyl ester of the title compound was confirmed. M/z: 564.24 (M+1) and 562.21 (MA). To the DCM solution of the previous reaction was added TFA (6 ml) and the mixture was stirred for 1 hour. The solvent was removed under reduced pressure and the residue was purified with preparative HPLC on a C8 column. A gradient from 20 to 70% ACN in 0.1M NH4OAc buffer was used as eluent. The pure fractions were collected and the MeCN was removed under reduced pressure. The remaining water solution was diluted with additional water and EtOAc. The water phase was acidified with KHSO4 (2M) to pH 2. The phases were separated and the organic phase was passed through a phase separator and concentrated. The oily residue was dissolved in MeCN and water. After lyophilisation, the title compound was obtained. H-NMR (400 MHz, DMSO-d6): 3.17 (t, 2H), 4.23 (ABq, 2H), 4.28 (d, 1H), 4.52 (b, 2H), 4.59 (t, 2H), 5.11 (d, 1H), 6.78-6.88 (m, 3H), 7.09-7.15 (m, 2H) 7.16-7.22 (m, 2H), 7.30 (d, 2H), 7.71-7.76 (m, 1H), 7.79 (s, 1H). M/z: 508.13 (M+1) and 506.22 (M−1).

후처리

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe crude thiol was dissolved in DCM (12 ml)
  3. additionEt3N, (30 pd, 0.22 mmol) was added
  4. waitAfter 5 minutes
  5. stirringthe reaction mixture was stirred overnight
  6. stirringthe reaction mixture was stirred for 1 hour

출처 및 근거

ORD 기록
ord-179dab318c614435b77c054c2d38d739
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07893048B2

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