Dimethylformamide → n-Methyl-10-{[2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-n-[(1-oxidopyridin-3-yl)methyl]-10,11-dihydro-5h-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

HRID 1830055Notes

Reaction equation

HRID 1830055 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[C:21](C(O)=O)=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])[CH:5]=[CH:4][C:3]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]([F:36])([F:35])[F:34].[OH:37][N:38]1[C:42]2C=[CH:44][CH:45]=[CH:46][C:41]=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.[CH3:68][N:69]([CH3:72])[CH:70]=[O:71]>C(OCC)(=O)C>[CH3:68][N:69]([CH2:72][C:45]1[CH:44]=[N+:38]([O-:37])[CH:42]=[CH:41][CH:46]=1)[C:70]([C:21]1[N:13]2[C:12]([CH2:11][N:10]([C:8]([C:6]3[CH:5]=[CH:4][C:3]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[C:33]([F:36])([F:34])[F:35])=[C:2]([CH3:1])[CH:7]=3)=[O:9])[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14]2)=[CH:23][CH:22]=1)=[O:71]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1027808210-(2-methyl-2'-trifluoromethyl-biphenyl-4-carbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid

Product 1

HCID 10232599n-Methyl-10-{[2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-n-[(1-oxidopyridin-3-yl)methyl]-10,11-dihydro-5h-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of the 10-(2-methyl-2′-trifluoromethyl-biphenyl-4-carbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 1, Step F (0.50 g, 1.02 mmol), methyl-(1-oxy-pyridin-3-ylmethyl)-amine dihydrochloride of Step C (0.26 g, 1.23 mmol) and 1-hydroxybenzotriazole (0.16 g, 1.18 mmol) in N,N-dimethylformamide (4 mL) was added 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.21 g, 1.10 mmol) followed by N,N-diisopropylethyl amine (0.73 mL, 4.10 mmol). The reaction mixture was stirred overnight, diluted with ethyl acetate and washed with water and saturated aqueous sodium bicarbonate. The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography eluting with 2% methanol in chloroform provided 0.52 g of the title compound, which was redissolved in dichloromethane and concentrated in vacuo to give a white foam.

Workup

  1. washwashed with water and saturated aqueous sodium bicarbonate
  2. dry with materialThe organic phase was then dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a yellow foam
  6. customPurification by flash chromatography
  7. washeluting with 2% methanol in chloroform

Sources & evidence

ORD record
ord-29f8aae8865d44509c24817b6697e3c1
Source dataset
uspto-grants-2006_06
Patent number
US07064120B2

Reaction notes

Loading…