1-Hydroxybenzotriazole → N-Methyl-N-[3-(dimethylamino)propyl]-10-[(3-methoxy-2'-methyl[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

HRID 2215128Notes

Reaction equation

HRID 2215128 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[CH3:34])[CH:6]=[CH:7][C:8]=1[C:9]([N:11]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[CH2:15][N:14]2[C:22]([C:25]([OH:27])=O)=[CH:23][CH:24]=[C:13]2[CH2:12]1)=[O:10].ON1C2C=CC=CC=2N=N1.Cl.[CH3:46][N:47]([CH3:56])[CH2:48][CH2:49][CH2:50][N:51]=[C:52]=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH3:52][N:51]([CH2:50][CH2:49][CH2:48][N:47]([CH3:56])[CH3:46])[C:25]([C:22]1[N:14]2[C:13]([CH2:12][N:11]([C:9]([C:8]3[CH:7]=[CH:6][C:5]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[CH3:34])=[CH:4][C:3]=3[O:2][CH3:1])=[O:10])[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH2:15]2)=[CH:24][CH:23]=1)=[O:27]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1027581410-[(3-Methoxy-2'-methyl[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid

Product 1

HCID 10231007N-Methyl-N-[3-(dimethylamino)propyl]-10-[(3-methoxy-2'-methyl[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamideYield 74.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 10-[(3-methoxy-2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 10, Step F (0.40 g, 0.88 mmol), 3-(dimethylaminopropyl)-1-methyl amine (0.16 mL, 1.09 mmol) and 1-hydroxybenzotriazole (0.135 g, 0.96 mmol) in N,N-dimethylformamide (4 mL) was added 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.19 g, 1.09 mmol) followed by N,N-diisopropylethyl amine (0.24 mL, 1.35 mmol). The reaction mixture was stirred overnight, then 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 on silica gel using a solvent system of 5% methanol in dichloromethane afforded 0.36 g of title compound as 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 on silica gel using a solvent system of 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-2457ea9acb34468f96a10e2675e3ab1c
Source dataset
uspto-grants-2006_09
Patent number
US07109193B2

Reaction notes

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