Bis(2-oxo-3-oxazolidinyl)phosphinic chloride → {3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone

HRID 1865627노트

반응식

HRID 1865627 반응식
[Cl:1][C:2]1[C:3]([OH:28])=[C:4]([CH:8]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[N:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:10]=1)[C:5]([OH:7])=O.[CH2:29]([N:31]([CH2:40][CH3:41])[CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)[CH3:30].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(=O)(O)[O-].[Na+]>C(#N)C.CN(C=O)C.O.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([OH:28])=[C:4]([C:5]([N:37]2[CH2:38][CH2:39][N:34]([CH2:33][CH2:32][N:31]([CH2:40][CH3:41])[CH2:29][CH3:30])[CH2:35][CH2:36]2)=[O:7])[CH:8]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[N:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:10]=1

참가 물질

9

반응물 4

HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride2회HCID 516892Sodium BicarbonateHCID 2736105N,N-Diethyl-2-(piperazin-1-yl)ethan-1-amineHCID 1784893953-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-benzoic acid

생성물 1

HCID 178464031{3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone수율 17%

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

반응 조건

온도
75 °C

실험 절차

14 mg (35 mol) of 3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-benzoic acid and 22 μL (approx. 120 μmol; density unknown) of 1-(2-diethylaminoethyl)-piperazine were dissolved in a mixture of 1 mL of acetonitrile and 100 μL of DMF. 14 mg (55 μmol) of bis(2-oxo-3-oxazolidinyl)phosphinic chloride was added and the mixture heated gently until all materials were dissolved. The resulting solution was left at ambient temperature for 4.5 h. 28 mg (110 μmol) of bis(2-oxo-3-oxazolidinyl)phosphinic chloride was added and the resulting mixture left at ambient temperature for 3.5 h, then heated to 75° C. for 3.5 h. The resulting mixture was distributed between 1 mL of a saturated aqueous solution of sodium bicarbonate in water and 2 mL of ethyl acetate. The organic phase was evaporated and the residue directly purified by mass-triggered reverse-phase HPLC to afford 3.2 mg (5.7 μmol, 17%) of {3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ 13.80 (s, br. 1H), 8.81 (d, 1H), 8.29 (d, 1H), 7.82 (d, 1H), 7.64 (dd, 1H), 7.49-7.44 (m, 2H), 7.21 (d, 1H), 7.10 (ddd, 1H), 3.83 (s, 3H), 3.40-3.30 (m, 4H), 2.49-2.35 (m, 8H), 0.94 (t, 6H), MS: m/z 563.2 (M+H+).

후처리

  1. temperaturethe mixture heated gently until all materials
  2. dissolutionwere dissolved
  3. waitthe resulting mixture left at ambient temperature for 3.5 h
  4. customThe organic phase was evaporated
  5. customthe residue directly purified by mass-triggered reverse-phase HPLC

출처 및 근거

ORD 기록
ord-d85e36c0aaf64f72a99fdf84dd29896a
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07626021B2

반응 노트

불러오는 중…