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Triethylamine → 4,4,4-Trifluoro-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)butan-1-one

HRID 2062167
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HRID 2062167 반응식
[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[N:7][C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])=[N:9]2)=[CH:4][CH:3]=1.[F:25][C:26]([F:34])([F:33])[CH2:27][CH:28]([OH:32])[C:29](O)=[O:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.O>[F:25][C:26]([F:34])([F:33])[CH2:27][CH:28]([OH:32])[C:29]([N:22]1[CH2:23][CH2:24][N:19]([C:6]2[C:5]3[C:10](=[CH:11][C:2]([CH3:1])=[CH:3][CH:4]=3)[N:9]=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])[N:7]=2)[CH2:20][CH2:21]1)=[O:30]
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참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 198006174,4,4-Trifluoro-2-hydroxybutanoic acidHCID 1361346166-[7-methyl-4-(1-piperazinyl)-1H-quinazolin-2-ylidene]-1-cyclohexa-2,4-dienone

생성물 1

HCID 136121453
4,4,4-Trifluoro-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)butan-1-one
수율 69.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

2-(7-Methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol (87 mg, 0.27 mmol), 4,4,4-trifluoro-2-hydroxybutanoic acid (43 mg, 0.27 mmol), HATU (0.12 g, 0.33 mmol) and triethylamine (45 μL, 0.33 mmol) were stirred in DMF (3 mL) at room temperature overnight. The mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine and water, dried over Na2SO4 and concentrated. Purification via silica gel chromatography using 0-20% EtOAc in 1:1 CH2Cl2: hexanes gave 4,4,4-trifluoro-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)butan-1-one as an off-white solid (86 mg, 66%). 1H NMR (400 MHz, CDCl3) δ 8.46 (dd, J=8.0, 1.7 Hz, 1H), 7.77 (d, J=8.5 Hz, 1H), 7.70 (s, 1H), 7.41-7.37 (m, 1H), 7.31 (dd, J=8.5, 1.5 Hz, 1H), 7.05-7.03 (m, 1H), 6.97-6.93 (m, 1H), 4.80-4.75 (m, 1H), 4.07-3.68 (m, 9H), 2.56 (s, 3H), 2.50-2.39 (m, 2H); LC/MS: m/z 461.3 (M+H)+ at 2.49 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

후처리

  1. extractionextracted with EtOAc
  2. washThe combined organic layers were washed with brine and water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customPurification via silica gel chromatography

출처 및 근거

ORD 기록
ord-6aca3162e2a04c468bc65c9955183daf
출처 데이터셋
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08283354B2

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