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

HRID 75256

Reaction equation

HRID 75256 reaction equation
[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]

Participants

5

Reactant 4

HCID 8857Ethyl AcetateHCID 134664Benzodiazepine2×HCID 253877Potassium BromideHCID 21930961HCID 21930961, compound

Product 1

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

Procedure

{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).

Workup

  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.

Sources & evidence

ORD record
ord-e7ce759ee1ae4dd3b67dfb9865a12184
Source dataset
uspto-grants-2014_09
Patent number
US08835424B2

Linked notes

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