Acetic Acid → HCID 57404717、化合物

HRID 1622311ノート

反応式

HRID 1622311 の反応式
Cl.[NH2:2][OH:3].[OH-].[K+].NO.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18]([C:22]([N:24]2[CH2:33][CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[C:29]([C:34](OC)=[O:35])[CH:30]=3)[CH2:25]2)=[O:23])([CH3:21])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].C(O)(=O)C>CO.CN(C=O)C>[OH:3][NH:2][C:34]([C:29]1[CH:30]=[C:31]2[C:26](=[CH:27][CH:28]=1)[CH2:25][N:24]([C:22]([C:18]1([CH3:21])[CH2:19][CH2:20][N:15]([C:13]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:14])[CH2:16][CH2:17]1)=[O:23])[CH2:33][CH2:32]2)=[O:35]

参加物

8

反応物 5

HCID 176Acetic AcidHCID 787HydroxylamineHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 67979956HCID 67979956、化合物

生成物 1

HCID 57404717HCID 57404717、化合物収率 74.5%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒3 回HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

A mixture of hydroxylamine hydrochloride (2.0 g, 29 mmol) in methanol (10 mL) was heated at 90° C. under a dry nitrogen atmosphere until homogeneous. To this heated solution was added a solution of potassium hydroxide (2.85 g, 50.8 mmol) in methanol (6 mL). A precipitate formed on mixing. After heating at 90° C. for 30 minutes, the mixture was cooled to rt and the solids were allowed to settle. The resulting solution was assumed to contain 1.7 M hydroxylamine.potassium salt and was carefully removed by syringe to exclude solids. An aliquot of the above solution (1.95 mL, 3.31 mmol) was added to a solution of methyl 2-{[1-(tert-butoxycarbonyl)-4-methylpiperidin-4-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (138 mg, 0.331 mmol) in methanol (0.5 mL) and DMF (0.5 mL). After stirring for 3 h at rt, excess reagent was quenched by the addition of acetic acid (0.188 mL, 3.31 mmol). The mixture was concentrated to dryness and the residue was twice co-evaporated with toluene. The crude product was purified by preparative HPLC to afford tert-butyl 4-{[6-(hydroxycarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}-4-methylpiperidine-1-carboxylate (103 mg, 74.5%). LC-MS: (FA) ES+ 418; 1H NMR (400 MHz, DMSO) δ 11.03 (s, 1H), 9.00 (s, 1H), 7.59-7.52 (m, 2H), 7.28 (d, J=8.0 Hz, 1H), 4.71 (s, 2H), 3.79 (t, J=5.8 Hz, 2H), 3.53-3.44 (m, 2H), 3.15-3.03 (m, 2H), 2.83 (t, J=5.4 Hz, 2H), 2.06-1.96 (m, 2H), 1.47-1.39 (m, 2H), 1.37 (s, 9H), 1.24 (s, 3H).

後処理

  1. customA precipitate formed
  2. additionon mixing
  3. temperatureAfter heating at 90° C. for 30 minutes
  4. temperaturethe mixture was cooled to rt
  5. custompotassium salt and was carefully removed by syringe
  6. concentrationThe mixture was concentrated to dryness
  7. customThe crude product was purified by preparative HPLC

出典と根拠

ORDレコード
ord-35db433ea0ac451a8448ce1c08227a2c
出典データセット
uspto-grants-2014_07
特許番号
US08778931B2

反応ノート

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