Triethylamine → 3-[1-[4-(7-methyl-1H-indazol-5-yl)-3-pyridin-2-ylbutanoyl]piperidin-4-yl]-1,4-dihydroquinazolin-2-one

HRID 2099739ノート

反応式

HRID 2099739 の反応式
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][CH:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:13][C:14](O)=[O:15])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.N1([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[NH:32][C:31](=[O:39])[N:30]=2)CCCCC1.C(N(CC)CC)C.CCOP(ON1N=[N:65][C:60]2C=[CH:62][CH:63]=[CH:64][C:59]=2C1=O)(OCC)=O>C(Cl)Cl.C(OCC)(=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][CH:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:13][C:14]([N:65]2[CH2:62][CH2:63][CH:64]([N:30]3[CH2:29][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[NH:32][C:31]3=[O:39])[CH2:59][CH2:60]2)=[O:15])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2

参加物

7

反応物 4

HCID 8471TriethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 160374384-(7-methyl-1H-indazol-5-yl)-3-pyridin-2-yl-butyric acidHCID 541506284-piperidinyl-2(1H)-quinazolinone

生成物 1

HCID 114321833-[1-[4-(7-methyl-1H-indazol-5-yl)-3-pyridin-2-ylbutanoyl]piperidin-4-yl]-1,4-dihydroquinazolin-2-one収率 62%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 4-(7-methyl-1H-indazol-5-yl)-3-pyridin-2-yl-butyric acid (white solid, 0.028 mmol) in methylene chloride (2 mL) was added 3,4-dihydro-3-(4-piperidinyl-2(1H)-quinazolinone (7.2 mg, 0.031 mmol, 1.1 equiv). Triethylamine (30 μL) was added followed by 3-(diethoxyphosphoryloxy)-1,2,3-benzotriain-4(3H)-one (DEPBT, 9.4 mg, 0.031 mmol 1.1 equiv). The resulting yellow solution was stirred at room temperature for 1 h and LCMS. A further 1 equivalent of the amine and DEPBT were added. After stirring for another 4 h, LCMS indicated complete conversion. The reaction mixture was diluted with ethyl acetate and quenched with 0.5 N sodium hydroxide. The layers were separated and the organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography (10% methanol in methylene chloride) to afford the desired product (9.0 mg, 62% for two steps) as a glassy solid. MS (ESI) [M+H]+=509, 1H-NMR (400 MHz, CDCl3) δ 11.5 (br., 1H), 8.61-8.52 (m, 1H), 7.93 (d, J=4.8 Hz, 1H), 7.50-7.38 (m, 1H), 6.90 (m, 8H), 6.66 (d, J=7.6 Hz, 1H), 4.72-4.62 (m, 1H), 4.59-4.48 (m, 1H), 4.24 (s, 1H), 4.09 (s, 1H), 4.07-3.94 (m, 1H), 3.80-3.66 (m, 1H), 3.20-2.80 (m, 4H), 2.72-2.46 (m, 2H), 2.45 (d, J=4.8 Hz, 3H), 1.85-1.48 (m, 4H).

後処理

  1. stirringAfter stirring for another 4 h
  2. customquenched with 0.5 N sodium hydroxide
  3. customThe layers were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (10% methanol in methylene chloride)

出典と根拠

ORDレコード
ord-09d626fee53a4427b30b8381985f713b
出典データセット
uspto-grants-2009_08
特許番号
US07569578B2

反応ノート

読み込み中…