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

HRID 1362242ノート

反応式

HRID 1362242 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:20][C:21]1[C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26][C:22]=1[CH2:23]CN)[CH2:18][CH3:19].C1C=CC2N(O)N=[N:38][C:36]=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:38]([CH2:23][C:22]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH3:31])[C:21]=2[O:20][CH2:17][CH2:18][CH3:19])[CH3:36])=[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 10487224(2E)-3-(6-aminopyridin-3-yl)prop-2-enoic acidHCID 20982692(2-Propoxy-3-methoxy-benzyl)methylamine

生成物 1

HCID 66966932(E)-3-(6-Amino-pyridin-3-yl)-N-(2-propoxy-3-methoxy-benzyl)-N-methyl-acrylamide hydrochloride収率 47.2%

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 (E)-3-(6-amino-pyridin-3-yl)acrylic acid (164 mg, 1.0 mmol), (2-propoxy-3-methoxy-benzyl)methylamine (230 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; the residue was washed with ether and dried to afford the title compound (185 mg, 47%). 1H NMR (300 MHz, DMSO-d6) δ 8.16 (m, 3H), 7.48 and 7.45 (rotamers, 2d, J=15.4 Hz, 1H), 7.23 (d, J=15.4 Hz, 1H), 7.00 (m, 3H), 6.61 (m, 1H), 4.78 and 4.63 (rotamers, 2s, 2H), 3.87 (m, 2H), 3.79 (s, 3H), 3.09 and 2.85 (rotamers, 2s, 3H), 1.71 (m, 2H), 0.97 (m, 3H). MS (ESI) m/e 356 (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-bcc88efad2114a638a0a8b8f08240299
出典データセット
uspto-grants-2011_02
特許番号
US07879872B2

反応ノート

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