Triphenylphosphine → ethyl ((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 2235954노트

반응식

HRID 2235954 반응식
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][OH:12])[C:5]([CH3:13])=[CH:4][N:3]=1.[CH2:14]([O:16][C:17](=[O:29])[CH2:18][C@H:19]1[C:27]2[C:22](=[CH:23][C:24](O)=[CH:25][CH:26]=2)[CH2:21][CH2:20]1)[CH3:15].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[CH2:14]([O:16][C:17](=[O:29])[CH2:18][C@H:19]1[C:27]2[C:22](=[CH:23][C:24]([O:12][CH2:11][CH2:10][CH2:9][NH:8][C:6]3[C:5]([CH3:13])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=3)=[CH:25][CH:26]=2)[CH2:21][CH2:20]1)[CH3:15]

참가 물질

6

반응물 4

HCID 11776Triphenylphosphine2회HCID 730421,1'-(Azodicarbonyl)dipiperidine2회HCID 16110404ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetateHCID 593004463-[(2-Chloro-5-methyl-4-pyrimidinyl)amino]-1-propanol

생성물 1

HCID 59300503ethyl ((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate수율 99%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 3-[(2-chloro-5-methyl-4-pyrimidinyl)amino]-1-propanol (Example 339, 1.77 g, 8.81 mmol) and ethyl[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate Example 6, 970 mg, 8.81 mmol) in THF (33 mL) were added PPh3 (2.31 g, 8.81 mmol) and ADDP (2.22 g, 8.81 mmol). The reaction mixture was vigorously stirred at rt for 24 h, after which additional amounts of PPh3 (2.31 g, 8.81 mmol) and ADDP (2.22 g, 8.81 mmol) were added. After an additional 24 h, the reaction mixture was diluted with hexanes, filtered through Celite®, and the filtrate concentrated under reduced pressure. The residue was then purified by silica gel chromatography (2:1 to 1:1 hexanes/EtOAc) to give the product (1.70 g, 99%). 1H NMR (400 MHz, CDCl3) δ 1.29 (t, 3H), 1.75-1.80 (m, 1H), 2.02 (s, 3H), 2.12-2.18 (m, 2H), 2.38-2.46 (m, 2H), 2.72 (dd, 1H), 2.84-2.2.92 (m, 2H), 3.52-3.55 (m, 1H), 3.73 (q, 2H), 4.13 (t, 2H), 4.18 (q, 2H), 6.70 (d, 1H), 6.77 (s, 1H), 7.08 (d, 1H), 7.78 (s, 1H).

후처리

  1. waitAfter an additional 24 h
  2. filtrationfiltered through Celite®
  3. concentrationthe filtrate concentrated under reduced pressure
  4. customThe residue was then purified by silica gel chromatography (2:1 to 1:1 hexanes/EtOAc)

출처 및 근거

ORD 기록
ord-0bf1bba9cf8345c0bb5ad2a15650ffa8
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07714004B2

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