Pyridine → tert-Butyl N-[(1S)-1-(4-{2-[(2R)-2-methylbut-3-enamido]phenyl}pyridin-2-yl)but-3-en-1-yl]carbamate

HRID 1481289노트

반응식

HRID 1481289 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C@@H:14]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:15][CH:16]=[CH2:17])[CH:9]=1.[CH3:26][C@H:27]([CH:31]=[CH2:32])[C:28](O)=[O:29].N1C=CC=CC=1>CCOC(C)=O>[CH3:26][C@H:27]([CH:31]=[CH2:32])[C:28]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C@@H:14]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:15][CH:16]=[CH2:17])[CH:9]=1)=[O:29]

참가 물질

5

반응물 3

HCID 1049PyridineHCID 55299080(R)-2-methylbut-3-enoic acidHCID 68079321tert-Butyl N-[(1S)-1-[4-(2-aminophenyl)pyridin-2-yl]but-3-en-1-yl]carbamate

생성물 1

HCID 126739818tert-Butyl N-[(1S)-1-(4-{2-[(2R)-2-methylbut-3-enamido]phenyl}pyridin-2-yl)but-3-en-1-yl]carbamate수율 85%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 45D (1.4 g, 4.12 mmol), (R)-2-methylbut-3-enoic acid (0.58 g, 5.79 mmol) in EtOAc (41.2 ml) was added pyridine (1.001 ml, 12.37 mmol). The reaction was cooled down to 0° C. under Ar and propane phosphonic acid anhydride (4.91 ml, 8.25 mmol) was added dropwise. The reaction was then gradually warmed up to rt over night. The reaction mixture was diluted and washed with sat. aq. NaHCO3, aqueous layer back-extracted with EtOAc, combined EtOAc phase washed with brine, dried over MgSO4, filtered, concentrated. The residue was purified by silica gel chromatography to give the desired product (1.47 g, 85%) as an off white foam. 1H NMR (500 MHz, CHLOROFORM-d) δ 8.65-8.60 (m, 1H), 8.19 (d, J=8.3 Hz, 1H), 7.47-7.36 (m, 2H), 7.24-7.18 (m, 3H), 7.16 (dd, J=5.0, 1.4 Hz, 1H), 5.82-5.62 (m, 3H), 5.10-5.01 (m, 4H), 4.86 (d, J=7.2 Hz, 1H), 3.03 (quin, J=7.2 Hz, 1H), 2.62 (tq, J=14.1, 6.9 Hz, 2H), 1.49-1.36 (m, 9H), 1.25 (d, J=7.2 Hz, 3H). MS (ESI) m/z: 422.1 (M+H)+.

후처리

  1. additionwas added dropwise
  2. additionThe reaction mixture was diluted
  3. washwashed with sat. aq. NaHCO3, aqueous layer
  4. extractionback-extracted with EtOAc, combined EtOAc phase
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-4d4d23a5c367445aa01765f32f1211e3
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409908B2

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