Triethylamine → 4-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzamide hydrochloride

HRID 910996ノート

反応式

HRID 910996 の反応式
Cl.[Cl:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][C:4]=1[O:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[S:21][CH:22]=[C:23]([CH3:25])[N:24]=2)[CH:14]=1.C(N(CC)CC)C.C(Cl)(=O)OCC.[CH3:39][N:40]([CH3:44])[CH2:41][CH2:42][NH2:43].[OH-].[Na+]>CN(C=O)C>[ClH:2].[Cl:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:43][CH2:42][CH2:41][N:40]([CH3:44])[CH3:39])=[O:9])=[CH:5][C:4]=1[O:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[S:21][CH:22]=[C:23]([CH3:25])[N:24]=2)[CH:14]=1

参加物

7

反応物 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 66053N,N-DimethylethylenediamineHCID 248266634-Chloro-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzoic acid hydrochloride

生成物 1

HCID 248266654-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzamide hydrochloride収率 28.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

A 3 dram vial was charged with 4-chloro-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzoic acid hydrochloride (0.100 g, 0.2511 mmol), triethylamine (0.1016 g, 1.004 mmol) and DMF (3 mL). The reaction mixture was cooled to 0° C. and ethyl carbonochloridate (0.02641 mL, 0.2762 mmol) was added. The reaction mixture was at 0° C. for 3 hours. N,N-dimethylethylenediamine (0.04427 g, 0.5022 mmol) was added and the reaction mixture was stirred at room temperature overnight, and then 2N NaOH was added. The reaction mixture was extracted with ethyl acetate, dried over magnesium sulfate, filtered and concentrated. The residue was purified using prepacked silica gel column with 50% ethyl acetate in hexanes followed by 15% (ammoniated) methanol in ethyl acetate. 2M HCl in ether was added and the resulting solids were dried over high vacuum to afford 4-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzamide hydrochloride (0.017 g, 13.01% yield) as an off white solid. 1H NMR (DMSO) δ 11.21 (bs, 1H), 9.82 (bs, 1H), 8.95 (t, 1H), 8.24 (d, 1H), 7.90 (dd, 1H), 7.86 (d, 1H), 7.84 (d, 1H), 6.57 (m, 3H), 3.61 (q, 2H), 3.24 (q, 2H), 2.82 (s, 3H), 2.81 (s, 3H), 2.21 (d, 3H); Mass spectrum (esi) m/z=432 (100) (M+H—HCl).

後処理

  1. extractionThe reaction mixture was extracted with ethyl acetate
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified
  6. addition2M HCl in ether was added
  7. customthe resulting solids were dried over high vacuum

出典と根拠

ORDレコード
ord-92185b409cb7434b81442e40143714b3
出典データセット
uspto-grants-2011_09
特許番号
US08022222B2

反応ノート

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