Nitrogen → (S)-tert-butyl (4-(2-(3-cyano-4-fluorophenyl)thiazol-5-yl)-2,3-dihydro-1H-inden-1-yl)carbamate

HRID 1891461노트

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HRID 1891461 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]([O:20][C:21](=[O:41])[NH:22][C@@H:23]1[C:31]2[C:26](=[C:27](B3OC(C)(C)C(C)(C)O3)[CH:28]=[CH:29][CH:30]=2)[CH2:25][CH2:24]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>[C:16]([O:20][C:21](=[O:41])[NH:22][C@@H:23]1[C:31]2[C:26](=[C:27]([C:2]3[S:6][C:5]([C:7]4[CH:8]=[CH:9][C:10]([F:15])=[C:11]([C:12]#[N:13])[CH:14]=4)=[N:4][CH:3]=3)[CH:28]=[CH:29][CH:30]=2)[CH2:25][CH2:24]1)([CH3:19])([CH3:17])[CH3:18]

참가 물질

7

반응물 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 583671525-(5-Bromothiazol-2-yl)-2-fluorobenzonitrileHCID 58367258tert-Butyl (S)-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate

생성물 1

HCID 58367229(S)-tert-butyl (4-(2-(3-cyano-4-fluorophenyl)thiazol-5-yl)-2,3-dihydro-1H-inden-1-yl)carbamate수율 83%

시약·촉매·용매 2

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

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온도
80 °C

실험 절차

Prepared using General Procedure 4. A solution of 5-(5-bromothiazol-2-yl)-2-fluorobenzonitrile THZ INT-2 (2.0 g, 7.0 mmol), (S)-tert-butyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate IND INT-17 (2.5 g, 7.0 mmol), potassium carbonate (2.9 g, 21 mmol) and a 3:1 mixture of DME/H2O (30 mL) was degassed with N2 for 10 min before the addition of Pd(PPh3)4 (0.57 g, 0.005 mmol). The mixture was degassed with N2 for an additional 2 min and the suspension was heated under nitrogen at 80° C. for 12 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 3.0 g (83%) of (S)-tert-butyl(4-(2-(3-cyano-4-fluorophenyl)thiazol-5-yl)-2,3-dihydro-1H-inden-1-yl)carbamate as a white solid. LCMS-ESI (m/z) calculated for C24H22FN3O2S: 435.5; found 436.1 [M+H]+, tR=4.14 min. 1H NMR (400 MHz, CDCl3) δ 8.20 (m, 2H), 7.93 (s, 1H), 7.44 (d, J=7.5 Hz, 1H), 7.32 (m, 3H), 5.26 (m, 1H), 4.76 (d, J=8.4 Hz, 1H), 3.09 (m, 2H), 2.65 (ddd, J=12.5, 8.3, 4.6 Hz, 1H), 1.84 (dq, J=12.9, 8.5 Hz, 1H), 1.48 (s, 9H).

후처리

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

출처 및 근거

ORD 기록
ord-77ec342c72174f8e907eff1d9acfa669
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507538B2

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