1,2-Dichloroethane → (E)-3-(6-Amino-pyridin-3-yl)-N-(2-ethoxy-3-methoxy-benzyl)-N-methyl-acrylamide hydrochloride

HRID 1711922ノート

反応式

HRID 1711922 の反応式
C(Cl)C[Cl:3].[NH2:5][C:6]1[N:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14]([OH:16])=O)=[CH:8][CH:7]=1.[CH2:17]([O:19][C:20]1[C:28]([O:29][CH3:30])=[CH:27][CH:26]=[CH:25][C:21]=1[CH2:22]CN)[CH3:18].C1C=CC2N(O)N=[N:37][C:35]=2C=1.O.CCN(C(C)C)C(C)C.Cl>CN(C=O)C.O.C(Cl)Cl>[ClH:3].[NH2:5][C:6]1[N:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]([N:37]([CH2:22][C:21]2[CH:25]=[CH:26][CH:27]=[C:28]([O:29][CH3:30])[C:20]=2[O:19][CH2:17][CH3:18])[CH3:35])=[O:16])=[CH:8][CH:7]=1

参加物

10

反応物 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 47154242-(2-Ethoxy-3-methoxyphenyl)ethanamineHCID 534008323-(6-Aminopyridin-3-yl)prop-2-enoic acid

生成物 1

HCID 66966862(E)-3-(6-Amino-pyridin-3-yl)-N-(2-ethoxy-3-methoxy-benzyl)-N-methyl-acrylamide hydrochloride収率 46%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

EDC (231 mg, 1.2 mmol) was added to a solution of (−3-(6-amino-pyridin-3-yl)acrylic acid (164 mg, 1.0 mmol), (2-ethoxy-3-methoxy-benzyl)methylamine (215 mg, 1.1 mmol), HOBt H2O (149 mg, 1.1 mmol) and DIPEA (525 μL, 3.0 mmol) in dry DMF (10 mL). After 18 hr of stirring, the mixture was diluted with water (60 mL) and extracted with EtOAc (2×20 mL). The organic layer was washed with brine (2×30 mL), dried and evaporated. Flash chromatography (silica 1-3% MeOH in CH2Cl2) furnished pure free base which was dissolved in CH2Cl2 (10 mL). After addition of HCl (1.5 mL, 1M in ether), the solvents were evaporated and the residue was washed with ether and dried to afford the title compound (172 mg, 46%). 1H NMR (300 MHz, DMSO-d6) δ 8.28 (m, 3H), 7.48 and 7.45 (rotamers, 2d, J=15.4 Hz, 1H), 7.25 and 7.23 (rotamers, 2d, J=15.4 Hz, 11H), 7.00 (m, 3H), 6.62 (m, 1H), 4.78 and 4.63 (rotamers, 2s, 2H), 3.98 (m, 2H), 3.79 (s, 3H), 3.08 and 2.84 (rotamers, 2s, 3H), 1.28 (m, 3H). MS (ESI) m/e 342 (M+H)+.

後処理

  1. extractionextracted with EtOAc (2×20 mL)
  2. washThe organic layer was washed with brine (2×30 mL)
  3. customdried
  4. customevaporated
  5. customFlash chromatography (silica 1-3% MeOH in CH2Cl2) furnished pure free base which
  6. customthe solvents were evaporated
  7. washthe residue was washed with ether
  8. customdried

出典と根拠

ORDレコード
ord-084d564acc1f4761b5228bc8bccf10ec
出典データセット
uspto-grants-2010_09
特許番号
US07790709B2

反応ノート

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