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Triphenylphosphine → ethyl ((1S)-5-{3-[(6-chloro-5-cyano-3-fluoro-2-pyridinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 2235940
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HRID 2235940 반응식
[Cl:1][C:2]1[N:9]=[C:8]([N:10]([CH2:12][CH2:13][CH2:14][OH:15])[CH3:11])[C:7]([F:16])=[CH:6][C:3]=1[C:4]#[N:5].[CH2:17]([O:19][C:20](=[O:32])[CH2:21][C@H:22]1[C:30]2[C:25](=[CH:26][C:27](O)=[CH:28][CH:29]=2)[CH2:24][CH2:23]1)[CH3:18].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[Cl:1][C:2]1[N:9]=[C:8]([N:10]([CH3:11])[CH2:12][CH2:13][CH2:14][O:15][C:27]2[CH:26]=[C:25]3[C:30](=[CH:29][CH:28]=2)[C@H:22]([CH2:21][C:20]([O:19][CH2:17][CH3:18])=[O:32])[CH2:23][CH2:24]3)[C:7]([F:16])=[CH:6][C:3]=1[C:4]#[N:5]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 16110404ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetateHCID 866046002-Chloro-5-fluoro-6-[(3-hydroxypropyl)(methyl)amino]nicotinonitrile

생성물 1

HCID 86604602ethyl ((1S)-5-{3-[(6-chloro-5-cyano-3-fluoro-2-pyridinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate
수율 81%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 2-chloro-5-fluoro-6-[(3-ydroxypropyl)(methyl)amino]nicotinonitrile (Example 311) (0.50 g, 2.05 mmol) and ethyl [(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate (Example 6, 0.25 9, 1.14 mmol) in THF (9 mL) were added PPh3 (0.54 g, 2.05 mmol) and ADDP (0.52 g, 2.05 mmol) under argon. The golden yellow mixture was stirred at rt for 18 h, and then concentrated under reduced pressure. The product (0.41 g, 81%) was isolated after silica gel flash chromatography (2:1 hexanes/EtOAc). 1H NMR (400 MHz, CD2Cl2) δ 7.29 (d, 1H), 7.04 (d, 1H), 6.73 (d, 1H), 6.66 (dd, 1H), 4.16 (q, 2H), 3.99 (t, 2H), 3.82 (t, 2H), 3.51 (qt, 1H), 3.25 (d, 3H), 2.95-2.78 (m, 2H), 2.70 (dd, 1H), 2.45-2.32 (m, 2H), 2.12 (qt, 2H), 1.82-1.72 (m, 1H), 1.29 (t, 3H).

후처리

  1. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-eab274c693914032b5e2c2252596d0e6
출처 데이터셋
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07714004B2

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