Diisopropylethylamine → methyl 2-{8-chloro-2-[N-(3-(1,2,3,4-tetrahydropyridino[2,3-b]pyridin-7-yl)propyl)carbamoyl]-1H,3H,4H,5H-benzo[e]azepin-5-yl}acetate

HRID 1057514Notes

Reaction equation

HRID 1057514 reaction equation
[ClH:1].[C:2]([O:5][CH2:6]C)(=[O:4])[CH3:3].[C:8](Cl)(Cl)=[O:9].[C:12]1(C)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[NH:19]1[C:24]2=[N:25][C:26]([CH2:29][CH2:30][CH2:31][NH2:32])=[CH:27][CH:28]=[C:23]2[CH2:22][CH2:21][CH2:20]1.C([N:36]([CH2:40][CH3:41])[CH:37]([CH3:39])C)(C)C>>[Cl:1][C:17]1[CH:12]=[CH:13][C:14]2[CH:15]([CH2:3][C:2]([O:5][CH3:6])=[O:4])[CH2:41][CH2:40][N:36]([C:8](=[O:9])[NH:32][CH2:31][CH2:30][CH2:29][C:26]3[N:25]=[C:24]4[NH:19][CH2:20][CH2:21][CH2:22][C:23]4=[CH:28][CH:27]=3)[CH2:37][C:39]=2[CH:16]=1

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 98775993-(5,6,7,8-Tetrahydro-1,8-naphthyridin-2-yl)propan-1-amineHCID 19083224Phosgen tolueneHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 69157953methyl 2-{8-chloro-2-[N-(3-(1,2,3,4-tetrahydropyridino[2,3-b]pyridin-7-yl)propyl)carbamoyl]-1H,3H,4H,5H-benzo[e]azepin-5-yl}acetate

Conditions

Temperature
50 °C

Procedure

A solution of methyl 2-{2-[(tert-butyl)oxycarbonyl-8-chloro-1H,3H,4H,5H-benzo[e]azepin-5-yl}acetate (1 eq) in 1.17 M of HCl/ethyl acetate (30 eq) was stirred at room temperature for 18 hr. The reaction mixture was concentrated and dried under vacuum oven. The resulting residue was dissolved in methylene chloride (0.15 M) and followed by the addition of phosgene/toluene (20%) (10 eq) under nitrogen. After stirring for 1 hr, the solvent was removed by rotary evaporation. The residue was dissolved in 1 ml of N,N-dimethylformamide (0.07 M), followed by the addition of 3-(1,2,3,4-tetrahydropyridino[2,3-b]pyridin-7-yl)propylamine (2 eq) and N,N-diisopropylethylamine (10 eq). The reaction mixture was heated at 50° C. for 2 hr. The reaction solvent was removed by rotary evaporation and the residue was purified by flash chromatography (5% methanol/methylene chloride. EI-MS m/z 471 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customdried under vacuum oven
  3. dissolutionThe resulting residue was dissolved in methylene chloride (0.15 M)
  4. customthe solvent was removed by rotary evaporation
  5. dissolutionThe residue was dissolved in 1 ml of N,N-dimethylformamide (0.07 M)
  6. customThe reaction solvent was removed by rotary evaporation
  7. customthe residue was purified by flash chromatography (5% methanol/methylene chloride

Sources & evidence

ORD record
ord-72527742638549a38e123850f576bf01
Source dataset
uspto-grants-2003_02
Patent number
US06514964B1

Reaction notes

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