Triethylamine → 4-[1-(2-aminopyrimidin-4-yl)-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

HRID 1398669

반응식

HRID 1398669 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[N:7]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH2:22])[N:17]=3)[C:6]=2[CH:23]=1.[N:24]1[CH:29]=[CH:28][CH:27]=[N:26][C:25]=1[C:30]([OH:34])([C:32]#[CH:33])[CH3:31].C(N(CC)CC)C>CS(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:22][C:18]1[N:17]=[C:16]([N:7]2[C:6]3[CH:23]=[C:2]([C:33]#[C:32][C:30]([C:25]4[N:24]=[CH:29][CH:28]=[CH:27][N:26]=4)([OH:34])[CH3:31])[CH:3]=[CH:4][C:5]=3[N:9]=[C:8]2[O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[CH:21]=[CH:20][N:19]=1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 681815834-[6-bromo-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amineHCID 866695882-(Pyrimidin-2-yl)but-3-yn-2-ol

생성물 1

HCID 681817314-[1-(2-aminopyrimidin-4-yl)-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol수율 13%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
90 °C

실험 절차

A mixture of 4-[6-bromo-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine (150 mg, 0.31 mmol, 80% purity), 2-(pyrimidin-2-yl)but-3-yn-2-ol (300 mg, 2.02 mmol), bis(triphenylphosphine)palladium(II) dichloride (220 mg, 0.31 mmol) and triethylamine (2 mL) in dimethylsulfoxide (3 mL) was stirred for 1.5 hr at 90° C. under nitrogen. The reaction mixture was cooled to room temperature then filtered through a frit filter to remove the catalyst. The filtrate was purified by preparative HPLC to afford 18 mg (13%) of 4-[1-(2-aminopyrimidin-4-yl)-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol as a light brown solid: 1H NMR (400 MHz, DMSO) delta 8.89 (d, J=4.8 Hz, 2H), 8.44 (d, J=5.6 Hz, 1H), 8.12 (s, 1H), 7.51-7.48 (m, 2H), 7.28 (d, J=8.0 Hz, 1H), 7.16 (s, 2H), 6.85 (d, J=5.2 Hz, 1H), 6.13 (s, 1H), 5.36-5.29 (m, 2H), 1.89 (s, 3H); LC-MS: m/z=+456 (M+H)+.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationthen filtered through a frit
  3. filtrationfilter
  4. customto remove the catalyst
  5. customThe filtrate was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-9fef56e176e54629a6870d3deb91f1b6
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901313B2

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