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 1865627ノート

反応式

HRID 1865627 の反応式
[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

参加物

9

反応物 4

HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride2 回HCID 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

生成物 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]-methanone収率 17%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
75 °C

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-d85e36c0aaf64f72a99fdf84dd29896a
出典データセット
uspto-grants-2009_12
特許番号
US07626021B2

反応ノート

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