Nitrogen → (S)-5-(5-(1-((tert-butyldimethylsilyl)oxy)-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-fluorobenzonitrile

HRID 1891453ノート

反応式

HRID 1891453 の反応式
Br[C:2]1[S:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]([F:15])=[C:11]([CH:14]=2)[C:12]#[N:13])=[N:4][CH:3]=1.[C:16]([Si:20]([CH3:41])([CH3:40])[O:21][C@@H:22]1[C:30]2[C:25](=[C:26](B3OC(C)(C)C(C)(C)O3)[CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23]1)([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[K+].[K+].N#N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC.O>[Si:20]([O:21][C@@H:22]1[C:30]2[C:25](=[C:26]([C:2]3[S:6][C:5]([C:7]4[CH:8]=[CH:9][C:10]([F:15])=[C:11]([CH:14]=4)[C:12]#[N:13])=[N:4][CH:3]=3)[CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23]1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:41])[CH3:40]

参加物

7

反応物 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 583671525-(5-Bromothiazol-2-yl)-2-fluorobenzonitrileHCID 58367372(S)-tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)oxy)silane

生成物 1

HCID 58367337(S)-5-(5-(1-((tert-butyldimethylsilyl)oxy)-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-fluorobenzonitrile収率 60%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 18180031Water 1,2-dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

Prepared using General Procedure 1. A solution of 5-(5-bromothiazol-2-yl)-2-fluorobenzonitrile THZ INT-2 (0.12 g, 0.42 mmol), (5)-tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)oxy)silane IND INT-6 (0.16 g, 0.42 mmol), potassium carbonate (0.176 g, 1.2 mmol) and 3:1 mixture of DME/H2O (2 mL) was degassed with N2 for 10 min before the addition of Pd(PPh3)4 (0.034 g, 0.03 mmol). The mixture reaction was degassed with N2 for additional 2 min and then heated under microwave at 90° C. for 1.5 h. Upon cooling, the reaction mixture was diluted with EA (20 mL) and washed with brine (20 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by silica gel flash chromatography (30% EA/hexanes) to produce 0.116 g (60%) of (S)-5-(5-(1-((tert-butyldimethylsilyl)oxy)-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-fluorobenzonitrile as a white solid. LCMS-ESI (m/z) calculated for C25H27FN2OSSi: 450.6; found 451.1 [M+H]+, tR=4.86 min (Method 1). 1H NMR (400 MHz, CDCL3) δ 8.30-8.14 (m, 2H), 7.95 (s, 1H), 7.45 (dd, J=7.0, 0.9, 1H), 7.32 (ddd, J=23.9, 14.6, 11.0, 3H), 5.32 (t, J=7.0, 1H), 3.19 (ddd, J=15.9, 8.8, 2.7, 1H), 2.95 (dt, J=16.1, 8.1, 1H), 2.59-2.40 (m, 1H), 2.08-1.89 (m, 1H), 0.94 (s, 9H), 0.17 (dd, J=13.7, 7.8, 6H).

後処理

  1. customPrepared
  2. customThe mixture reaction
  3. customwas degassed with N2 for additional 2 min
  4. temperatureUpon cooling
  5. additionthe reaction mixture was diluted with EA (20 mL)
  6. washwashed with brine (20 mL)
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by silica gel flash chromatography (30% EA/hexanes)

出典と根拠

ORDレコード
ord-9784c35fe1af4ff49d6e905bccad0f56
出典データセット
uspto-grants-2013_08
特許番号
US08507538B2

反応ノート

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