1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-3-(2,2-Dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide hydrogen chloride

HRID 1362394Notes

Reaction equation

HRID 1362394 reaction equation
[CH3:1][NH:2][CH2:3][C:4]1[O:5][C:6]2[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=2[C:8]=1[CH3:9].[ClH:14].[CH3:15][C:16]1([CH3:31])[O:21][C:20]2[CH:22]=[C:23]([CH:26]=[CH:27][C:28]([OH:30])=O)[CH:24]=[N:25][C:19]=2[NH:18][CH2:17]1.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.CN(C)CCCN=C=NCC>CN(C=O)C.O>[ClH:14].[CH3:31][C:16]1([CH3:15])[O:21][C:20]2[CH:22]=[C:23](/[CH:26]=[CH:27]/[C:28]([N:2]([CH3:1])[CH2:3][C:4]3[O:5][C:6]4[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=4[C:8]=3[CH3:9])=[O:30])[CH:24]=[N:25][C:19]=2[NH:18][CH2:17]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 46785639N-methyl-1-(3-methylbenzofuran-2-yl)methanamineHCID 669677313-(2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acid hydrochloride

Product 1

HCID 16659990(E)-3-(2,2-Dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide hydrogen chloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl-(3-methyl-benzofuran-2-ylmethyl)-amine (88 mg, 0.5 mmol) in DMF (5 mL) were added in sequential order 3-(2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acid hydrochloride (107 mg, 0.46 mmol), 1-hydroxybenzotriazole (68 mg, 0.5 mmol), diisopropylethylamine (240 uL, 1.38 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (100 mg, 0.5 mmol). The mixture was stirred at room temperature overnight, cooled in an ice bath and water added with rapid stirring. The product was extracted with ethyl acetate (3×10 mL), dried with sodium sulfate, filtered and concentrated. The free base was re-solvated in methylene chloride (5 mL) and a solution of 4M HCl in dioxane (1 mL) was added to precipitate the hydrogen chloride salt as a pale yellow solid (84 mg, 43%): 1H NMR (400 MHz, DMSO-d6) δ 8.94 (1s, 1H), 8.01-8.06 (m, 2H), 7.47-7.58 (m, 3H), 7.16-7.25 (m, 3H), 4.73-4.94 (rotamers, 2s, 2H), 3.42 (s, 2H), 3.04 (s, 3H), 2.42 (s, 3H), 1.34 (s, 6H); MS (ESI) m/e 392 (C23H25N3O3+H)+.

Workup

  1. temperaturecooled in an ice bath
  2. extractionThe product was extracted with ethyl acetate (3×10 mL)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additiona solution of 4M HCl in dioxane (1 mL) was added
  7. customto precipitate the hydrogen chloride salt as a pale yellow solid (84 mg, 43%)

Sources & evidence

ORD record
ord-94d20d39f17d4761ad104644f434096f
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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