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

HRID 1891453노트

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HRID 1891453 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 18180031Water 1,2-dimethoxyethane용매

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온도
90 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-9784c35fe1af4ff49d6e905bccad0f56
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507538B2

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