Acetonitrile, 2-(methylamino)- → N-cyanomethyl-2-hydroxy-2-{3-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-5-yl]-phenyl}-N-methyl-acetamide

HRID 886617

反応式

HRID 886617 の反応式
[OH:1][CH:2]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:13]=[C:14]3[C:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][CH3:28])=[N:19][N:18](CO)[C:15]3=[N:16][CH:17]=2)[CH:7]=1)[C:3]([OH:5])=O.[CH3:31][NH:32][CH2:33][C:34]#[N:35].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[C:34]([CH2:33][N:32]([CH3:31])[C:3](=[O:5])[CH:2]([OH:1])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:13]=[C:14]3[C:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][CH3:28])=[N:19][NH:18][C:15]3=[N:16][CH:17]=2)[CH:7]=1)#[N:35]

参加物

6

反応物 3

HCID 36652Acetonitrile, 2-(methylamino)-HCID 81531DiisopropylethylamineHCID 59825038hydroxy-{3-[1-hydroxymethyl-3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid

生成物 1

HCID 178489384N-cyanomethyl-2-hydroxy-2-{3-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-5-yl]-phenyl}-N-methyl-acetamide収率 53%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of hydroxy-{3-[1-hydroxymethyl-3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid (0.1 g, 0.25 mmol), methylaminoacetonitrile (20 μl, 0.27 mmol), diisopropylethylamine (DIEA, 87 μl, 0.48 mmol), N,N,N′,N′,-Tetramethyl-O-(7-azabenotriazol-1-yl)uronium hexafluorophosphate (HATU, 101 mg, 0.27 mmol) in DMF (3 ml) was stirred at room temperature overnight. The reaction mixture was dissolved in 10 ml ethyl acetate and subsequently extracted with 1N HCl, saturated NaHCO3, brine, dried with Na2SO4, concentrated to dryness. The crude was purified by silica gel chromatography. The resulting material was dissolved in 3 ml of methanol, aqueous NaOH was added (1 ml, 2 N in H2O) and the mixture stirred overnight at room temperature. The solvent was removed under reduced pressure and the crude was neutralized with 500 μl of 1N HCl and purified by mass-triggered reverse phase HPLC to afford N-cyanomethyl-2-hydroxy-2-{3-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-5-yl]-phenyl}-N-methyl-acetamide as a yellow powder (56 mg, 53% yield). 1H NMR (500 MHz, DMSO-d6) δ 3.02 (s, 3H), 3.87 (s, 3H), 4.14 (s, 2H), 5.55 (s, 1H), 7.10 (m, 1H), 7.23 (d, 1H), 7.40 (d, 1H), 7.45-7.52 (m, 2H), 7.66 (d, 1H), 7.72 (m, 2H), 8.32 (s, 1H), 8.33 (s, 1H). MS: m/z 427.5 (M+H+).

後処理

  1. extractionsubsequently extracted with 1N HCl, saturated NaHCO3, brine
  2. dry with materialdried with Na2SO4
  3. concentrationconcentrated to dryness
  4. customThe crude was purified by silica gel chromatography
  5. dissolutionThe resulting material was dissolved in 3 ml of methanol
  6. additionaqueous NaOH was added (1 ml, 2 N in H2O)
  7. stirringthe mixture stirred overnight at room temperature
  8. customThe solvent was removed under reduced pressure
  9. custompurified by mass-triggered reverse phase HPLC

出典と根拠

ORDレコード
ord-ba58d341247946c7ba054bbaea5b696e
出典データセット
uspto-grants-2012_08
特許番号
US08242280B2

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