1,2-Dichloroethane → 4-(5-bromo-2-chloropyrimidin-4-yl)-N-((R)-1-(4-chlorophenyl)ethyl)morpholine-3-carboxamide

HRID 1631721ノート

反応式

HRID 1631721 の反応式
[Br:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH:10]2[C:15]([OH:17])=O)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([C@H:39]([NH2:41])[CH3:40])=[CH:35][CH:34]=1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH:10]2[C:15]([NH:41][C@@H:39]([C:36]2[CH:37]=[CH:38][C:33]([Cl:32])=[CH:34][CH:35]=2)[CH3:40])=[O:17])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 1715226(1R)-1-(4-chlorophenyl)ethan-1-amineHCID 86670107HCID 86670107、化合物

生成物 1

HCID 866701084-(5-bromo-2-chloropyrimidin-4-yl)-N-((R)-1-(4-chlorophenyl)ethyl)morpholine-3-carboxamide収率 40.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

4-(5-Bromo-2-chloropyrimidin-4-yl)morpholine-3-carboxylic acid (PREPARATION x30, 1 g, 3.10 mmol), EDC (0.892 g, 4.65 mmol), HOBt (0.712 g, 4.65 mmol), (R)-1-(4-chlorophenyl)ethanamine (0.724 g, 4.65 mmol) and triethylamine (1.296 mL, 9.30 mmol) were dissolved in DMF (15 mL). The resulting brown solution was stirred at room temperature for 18 hours and was subsequently diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×25 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give a crude product which was loaded onto an ISCO® silica gel cartridge (40 g) and eluted using an ethyl acetate/hexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a yellow foam (574 mg, 40%). 1H NMR (400 MHz, DMSO-d6) δ 1.38 (dd, J=7.07, 4.29 Hz, 3H), 3.55 (d, J=6.32 Hz, 2H), 3.68-3.79 (m, 1H), 3.84-3.91 (m, 1H), 4.22-4.39 (m, 2H), 4.86 (m, 1H), 4.89-5.03 (m, 1H), 7.31-7.41 (m, 4H), 8.45 (d, J=10.61 Hz, 2H).

後処理

  1. washwashed with aqueous saturated NH4Cl (3×25 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a crude product which
  6. washeluted
  7. customThe product was collected
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-fa7389bd5dc24c38ba2fbf5f6c7ef0c9
出典データセット
uspto-grants-2014_07
特許番号
US08791107B2

反応ノート

読み込み中…