Hydrochloric Acid → Diethyl (4-{[4-({7-[1-(2-hydroxyethyl)-1H-pyrazol-3-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrim idin-2-yl]amino}benzyl)phosphonate

HRID 511343

반응식

HRID 511343 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:13][C:14]2[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]3[CH:39]=[CH:38][C:28]([CH2:29][P:30](=[O:37])([O:34][CH2:35][CH3:36])[O:31][CH2:32][CH3:33])=[CH:27][CH:26]=3)[N:15]=2)=[C:6]2[C:10]=1[CH2:9][N:8]([CH3:11])[C:7]2=[O:12].[Si]([O:47][CH2:48][CH2:49][N:50]1[CH:54]=[CH:53][C:52](B(O)O)=[N:51]1)(C(C)(C)C)(C)C.Cl>C(Cl)Cl.O1CCOCC1>[OH:47][CH2:48][CH2:49][N:50]1[CH:54]=[CH:53][C:52]([C:2]2[CH:3]=[CH:4][C:5]([NH:13][C:14]3[C:19]([C:20]([F:21])([F:22])[F:23])=[CH:18][N:17]=[C:16]([NH:24][C:25]4[CH:26]=[CH:27][C:28]([CH2:29][P:30](=[O:37])([O:31][CH2:32][CH3:33])[O:34][CH2:35][CH3:36])=[CH:38][CH:39]=4)[N:15]=3)=[C:6]3[C:10]=2[CH2:9][N:8]([CH3:11])[C:7]3=[O:12])=[N:51]1

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 58292897Diethyl [4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonateHCID 67260822HCID 67260822, 화합물2회

생성물 1

HCID 58292998Diethyl (4-{[4-({7-[1-(2-hydroxyethyl)-1H-pyrazol-3-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrim idin-2-yl]amino}benzyl)phosphonate

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

실험 절차

The title compound was prepared according to the procedure for Compound 97A diethyl [4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate (30.0 mg, 0.0477 mmol) and [1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1H-pyrazol-3-yl]boronic acid (Compound 142A, 46.7 mg, 0.173 mmol). The afforded intermediate, diethyl (4-{[4-({7-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1H-pyrazol-3-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate, was purified using an ISCO Combiflash system (eluting with 0-100% EtOAc:CH2Cl2). The product thus obtained was dissolved in CH2Cl2 (2 mL), treated with 4.0 M of HCl in dioxane (0.5 mL) and stirred at rt for 2 h. The solid was filtered off and rinsed with a mixture of CH2Cl2/heptane, giving the title material as an off-white solid, 24.6 mg (77%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.89 (s, 1H), 10.03 (br s, 1H), 8.89 (br s, 1H), 8.49 (s, 1H), 7.91 (d, J=8.6 Hz, 1H), 7.81 (d, J=2.3 Hz, 1H), 7.57 (br s, 2H), 7.30 (br d, J=6.6 Hz, 2H), 6.93 (br s, 1H), 4.72 (s, 2H), 4.21 (t, J=5.6 Hz, 2H), 3.97 (quin, J=7.4 Hz, 4H), 3.81 (t, J=5.7 Hz, 2H), 3.25 (d, J=21.5 Hz, 2H), 3.13 (s, 3H), 1.16 (t, J=7.1 Hz, 6H). MS (ES+): m/z 660.22 (100) [MH+]. HPLC: tR=2.72 min (ZQ3, nonpolar—5 min).

후처리

  1. customThe afforded intermediate, diethyl (4-{[4-({7-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1H-pyrazol-3-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate, was purified
  2. washan ISCO Combiflash system (eluting with 0-100% EtOAc:CH2Cl2)
  3. customThe product thus obtained
  4. filtrationThe solid was filtered off
  5. washrinsed with a mixture of CH2Cl2/heptane

출처 및 근거

ORD 기록
ord-0ca93993cc524b73be47bba789b0cd22
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096624B2

연결된 노트

불러오는 중…