N-Methyl-D-glucamine → 10-[(2'-Methoxy-2-methyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid methyl-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxy-hexyl)-amide

HRID 2184448Notes

Reaction equation

HRID 2184448 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]([N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21][N:20]3[C:28]([C:31](O)=[O:32])=[CH:29][CH:30]=[C:19]3[CH2:18]2)=[O:16])=[CH:11][C:10]=1[CH3:34].[CH3:35][NH:36][CH2:37][C@@H:38]([C@H:40]([C@@H:42]([C@@H:44]([CH2:46][OH:47])[OH:45])[OH:43])[OH:41])[OH:39].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH3:35][N:36]([CH2:37][C@H:38]([OH:39])[C@@H:40]([OH:41])[C@H:42]([OH:43])[C@H:44]([OH:45])[CH2:46][OH:47])[C:31]([C:28]1[N:20]2[C:19]([CH2:18][N:17]([C:15]([C:12]3[CH:13]=[CH:14][C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[C:10]([CH3:34])[CH:11]=3)=[O:16])[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21]2)=[CH:30][CH:29]=1)=[O:32]

Participants

8

Reactant 5

HCID 8567N-Methyl-D-glucamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 1027581310-[(2'-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 980940110-[(2'-Methoxy-2-methyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid methyl-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxy-hexyl)-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 10-[(2′-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 14, Step E (0.70 g, 1.55 mmol), N-methyl-D-glucamine (0.36 g, 1.84 mmol) and 1-hydroxybenzotriazole monohydrate (0.23 g, 1.72 mmol) in N,N-dimethylformamide (6 mL) wad added 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.33 g, 1.72 mmol) followed by N,N-diisopropylethyl amine (0.41 mL, 2.30 mmol). The reaction mixture was stirred overnight, then was 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 10% methanol in chloroform provided the title compound, which was redissolved in dichloromethane and evaporated to dryness in vacuo to a pale, yellow foam (0.63 g).

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 10% methanol in chloroform

Sources & evidence

ORD record
ord-abc3289b9ad84d139c3b4ec39d1664af
Source dataset
uspto-grants-2005_05
Patent number
US06900200B2

Reaction notes

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