Ethyl Acetate → 8-Ethynyl-4-methyl-6-phenyl-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester

HRID 75256

反応式

HRID 75256 の反応式
[K+].[Br-].Br[C:4]1[CH:5]=[CH:6][C:7]2[N:13]3[CH:14]=[N:15][C:16]([C:17]([O:19][C:20](C)(C)[CH3:21])=[O:18])=[C:12]3[CH2:11][N:10]=[C:9]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:8]=2[CH:30]=1.N1C2C=CC=CC=2C=[CH:34][CH:33]=N1.[CH3:42]COC(C)=O>>[CH2:20]([O:19][C:17]([C:16]1[N:15]=[CH:14][N:13]2[C:12]=1[CH:11]([CH3:42])[N:10]=[C:9]([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:8]1[CH:30]=[C:4]([C:33]#[CH:34])[CH:5]=[CH:6][C:7]2=1)=[O:18])[CH3:21]

参加物

5

反応物 4

HCID 8857Ethyl AcetateHCID 134664Benzodiazepine2 回HCID 253877Potassium BromideHCID 21930961HCID 21930961、化合物

生成物 1

HCID 730213258-Ethynyl-4-methyl-6-phenyl-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester

実験手順

{1-[4-Bromo-2-(2-fluoro-benzoyl)-phenylcarbamoyl-ethyl}-carbamic acid tert-butyl ester 116. To a stirred solution of (2-amino-5-bromophenyl)-(2-fluoro-phenyl)-methanone (60 g, 204 mmol) 115 and the N-Boc-L-alanine 107 (38.59 g, 204 mmol) in CH2Cl2 (500 mL) was added dicyclohexylcarbodiimide (DCC) (42.09 g, 204 mmol) in CH2Cl2 (200 mL) dropwise, over a 30 min period at 0° C. The reaction mixture was allowed to stir an additional 8 h at rt. The dicyclohexyl urea which formed was filtered off and the filtrate concentrated under reduced pressure. The crude solid residue 116 was purified by recrystallization from hexane and EtOAc to afford 116 (74.9 g, 79%) mp 158-159° C.; IR (KBr, cm−1) 3332, 2931, 255, 1694, 1643, 1613, 1582, 1537, 1450; 1H NMR (CDCl3) δ 11.68 (s, 1 H), 8.71 (d, J=9.0 Hz, 1 H), 7.69 (dd, J=9.0, 2.3 Hz, 1 H), 7.55-7.62 (m, 2 H), 7.46 (td, J=7.6, 1.4 Hz, 1 H), 7.30 (t, J=7.5 Hz, 1 H), 7.21 (t, J=9.1 Hz, 1 H), 5.13 (b, 1 H), 4.37 (b, 1 H), 1.51 (d, J=7.2 Hz, 3 H), 1.45 (s, 9H). MS (EI) m/e (relative intensity) 467 (M++2, 14), 466 (M++1, 44), 465 (M+, 14), 464 (42), 329 (15), 321 (60), 295 (100), 224 (26); [α]26D=−59.1 (c 0.51, EtOAc).

後処理

  1. filtrationwas filtered off
  2. concentrationthe filtrate concentrated under reduced pressure
  3. customThe crude solid residue 116 was purified by recrystallization from hexane and EtOAc
  4. customto afford 116 (74.9 g, 79%) mp 158-159° C.

出典と根拠

ORDレコード
ord-e7ce759ee1ae4dd3b67dfb9865a12184
出典データセット
uspto-grants-2014_09
特許番号
US08835424B2

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