1,2-Dichloroethane → Benzyl 4-(5-chloro-3-(((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenoxy)piperidine-1-carboxylate

HRID 1050448ノート

反応式

HRID 1050448 の反応式
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[C:19]([CH3:28])=[C:20]([CH:24]=[C:25]([Cl:27])[CH:26]=2)[C:21](O)=[O:22])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:30][CH2:31][C:32]1[C:37](=[O:38])[CH:36]=[C:35]([CH3:39])[NH:34][C:33]=1[CH3:40].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C([O-])(O)=O.[Na+]>O.CN(C)C=O>[Cl:27][C:25]1[CH:24]=[C:20]([C:21](=[O:22])[NH:30][CH2:31][C:32]2[C:37](=[O:38])[CH:36]=[C:35]([CH3:39])[NH:34][C:33]=2[CH3:40])[C:19]([CH3:28])=[C:18]([CH:26]=1)[O:17][CH:14]1[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12][CH2:13]1

参加物

9

反応物 6

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 902732273-(aminomethyl)-2,6-dimethylpyridin-4(1H)-one hydrochlorideHCID 902733993-((1-((Benzyloxy)carbonyl)piperidin-4-yl)oxy)-5-chloro-2-methylbenzoic acid

生成物 1

HCID 76901950Benzyl 4-(5-chloro-3-(((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenoxy)piperidine-1-carboxylate収率 64.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A 20 mL vial containing 3-((1-((benzyloxy)carbonyl)piperidin-4-yl)oxy)-5-chloro -2-methylbenzoic acid (35.0 mg, 0.087 mmol) was charged with 3-(aminomethyl)-2,6-dimethylpyridin-4(1H)-one hydrochloride (17.98 mg, 0.095 mmol), EDC (24.92 mg, 0.130 mmol), HOAt (20.04 mg, 0.130 mmol), N,N-dimethylformamide (1 mL), N-methylmorpholine (0.143 mL, 1.300 mmol) and a magnetic stir bar. The vial was capped and the reaction was stirred at room temperature for 3 days, at which time it was dripped into a stirred solution of saturated NaHCO3 (20 mL) and water (5 mL). The suspension was stirred at room temperature for 20 min and the solid was collected via vacuum filtration and dried under high vacuum. Purification of the solid by reverse phase HPLC (Column: Phenomenex Gemini-NX axia, 30×100, 5μ, C18. Eluent:10-80% acetonitrile/0.1% formic acid in water, 7 min gradient) gave benzyl 4-(5-chloro-3-(((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenoxy)piperidine-1-carboxylate (30 mg, 0.056 mmol, 64.3% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 8.21 (t, J=5.05 Hz, 1H), 7.26-7.44 (m, 5H), 7.15 (d, J=2.02 Hz, 1H), 6.81 (d, J=2.02 Hz, 1H), 5.87 (s, 1H), 5.09 (s, 2H), 4.70 (br. s., 1H), 4.19 (d, J=5.05 Hz, 2H), 3.63 (br. s., 2H), 3.36-3.45 (m, 2H), 2.31 (s, 3H), 2.15 (s, 3H), 2.06 (s, 3H), 1.90 (d, J=12.88 Hz, 2H), 1.49-1.67 (m, 2H). MS(ES) [M+H]+ 538.3.

後処理

  1. customThe vial was capped
  2. stirringThe suspension was stirred at room temperature for 20 min
  3. filtrationthe solid was collected via vacuum filtration
  4. customdried under high vacuum
  5. customPurification of the solid by reverse phase HPLC (Column: Phenomenex Gemini-NX axia, 30×100, 5μ, C18. Eluent:10-80% acetonitrile/0.1% formic acid in water, 7 min gradient)

出典と根拠

ORDレコード
ord-7bb64183ce834911b43f13b9a9d3c079
出典データセット
uspto-grants-2016_07
特許番号
US09382234B2

反応ノート

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