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Tributylphosphine → methyl 2-((4S,5S)-1-(4-(((3R,4R)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate

HRID 2278686
ノート
印刷プレビュー

反応式

HRID 2278686 の反応式
[Cl:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][C@@H:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[C@@H:27]([CH2:28][C:29]([O-:31])=[O:30])[C@H:26]([CH3:32])[C:25]([C:33]([F:36])([F:35])[F:34])=[N:24]4)=[CH:19][CH:18]=3)[C@H:12]([CH3:37])[CH2:11]2)=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.O[C:39]1C=CC(N2[C@@H](CC(OC)=O)[C@H](C)C(C(F)(F)F)=N2)=CC=1.ClC1C(N2CC[C@H](O)[C@H](C)C2)=CC(OC)=NC=1.C(P(CCCC)CCCC)CCC.N(/C(N1CCCCC1)=O)=N\C(N1CCCCC1)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][C@@H:13]([O:16][C:17]3[CH:18]=[CH:19][C:20]([N:23]4[C@@H:27]([CH2:28][C:29]([O:31][CH3:39])=[O:30])[C@H:26]([CH3:32])[C:25]([C:33]([F:36])([F:34])[F:35])=[N:24]4)=[CH:21][CH:22]=3)[C@H:12]([CH3:37])[CH2:11]2)=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 13831TributylphosphineHCID 5702657diazenedicarboxylic acid bis(N,N-piperidide)HCID 867194222-((4S,5S)-1-(4-(((3R,4R)-1-(5-Chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetateHCID 86719423methyl 2-((4S,5S)-1-(4-hydroxyphenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate
HCID 86719424
(3R,4S)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-ol

生成物 1

HCID 86719421methyl 2-((4S,5S)-1-(4-(((3R,4R)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate収率 64%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
50 °C

実験手順

2-((4S,5S)-1-(4-(((3R,4R)-1-(5-Chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate: To a solution of methyl 2-((4S,5S)-1-(4-hydroxyphenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate (1J, 4.6 g, 15 mmol) and (3R,4S)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-ol (3.4 g, 13 mmol) in toluene (166 mL) was added tributylphosphine (5.5 mL, 21 mmol). While stirring, (E)-diazene-1,2-diylbis(piperidin-1-ylmethanone) (5.4 g, 21 mmol) was added portionwise to the reaction mixture, and the resulting mixture was heated at 50° C. for 120 min. The mixture was cooled to rt and 150 mL of hexanes was added to the mixture and a white precipitate formed. The mixture was filtered, and the filtrate was concentrated and was purified via silica gel chromatography to give methyl 2-((4S,5S)-1-(4-(((3R,4R)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate (4.7 g, 8.5 mmol, 64% yield). LC-MS Anal. Calc'd for C26H30ClF3N4O4 554.19. found [M+H] 555.2. 1H NMR (400 MHz, CDCl3) δ ppm 8.00 (s, 1H), 7.15-7.04 (m, 2H), 7.01-6.89 (m, 2H), 6.30 (s, 1H), 4.49-4.36 (m, 1H), 3.91 (s, 4H), 3.73 (s, 3H), 3.62-3.49 (m, 2H), 3.28-3.15 (m, 1H), 2.95-2.85 (m, 1H), 2.82 (dd, J=16.2, 3.2 Hz, 1H), 2.67 (dd, J=12.3, 9.0 Hz, 1H), 2.43 (dd, J=16.1, 10.3 Hz, 1H), 2.26-2.12 (m, 2H), 1.91-1.78 (m, 1H), 1.36 (d, J=7.0 Hz, 3H), 1.16 (d, J=6.6 Hz, 3H).

後処理

  1. temperatureThe mixture was cooled to rt
  2. customa white precipitate formed
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate was concentrated
  5. customwas purified via silica gel chromatography

出典と根拠

ORDレコード
ord-371321e345c1431aa90d9d11e9af3457
出典データセット
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09133163B2

反応ノート

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