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

HRID 2184458Notes

Reaction equation

HRID 2184458 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([N:11]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH2:15][N:14]3[C:22]([C:25]([OH:27])=O)=[CH:23][CH:24]=[C:13]3[CH2:12]2)=[O:10])[CH:6]=[CH:5][C:4]=1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]([F:37])([F:36])[F:35].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH3:60][NH:61][CH2:62][CH:63]([OH:66])[CH2:64][OH:65]>CN(C)C=O.O>[OH:66][CH:63]([CH2:64][OH:65])[CH2:62][N:61]([CH3:60])[C:25]([C:22]1[N:14]2[C:13]([CH2:12][N:11]([C:9]([C:7]3[CH:6]=[CH:5][C:4]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[C:34]([F:37])([F:35])[F:36])=[C:3]([O:2][CH3:1])[CH:8]=3)=[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 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27341223-(Methylamino)propane-1,2-diolHCID 2194775510-{[2-methoxy-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid

Product 1

HCID 10145231N-(2,3-Dihydroxypropyl)-10-{[2-methoxy-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-N-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamideYield 30.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of the 10-{[2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step E (0.300 g, 0.65 mmol)) in N,N-dimethylformamide (15 mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.150 g, 0.78 mmol) and 1-hydroxybenzotriazole (0.110 g, 0.78 mmol). After the solution became homogeneous 3-methylamino-1,2-propanediol (0.082 g, 0.78 mmol) was added, and the solution was stirred at room temperature overnight. The mixture was then poured into water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried and concentrated to dryness. The residue was subjected to silica chromatography eluting with 10% methanol in chloroform. The pure fractions were concentrated and the residue azeotroped and triturated several times with hexane to provide the title product (0.118 g) as a white solid, m.p. 119-123° C.

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate
  3. washThe combined ethyl acetate layers were washed with water
  4. customdried
  5. concentrationconcentrated to dryness
  6. washeluting with 10% methanol in chloroform
  7. concentrationThe pure fractions were concentrated
  8. customthe residue azeotroped
  9. customtriturated several times with hexane

Sources & evidence

ORD record
ord-810acad94e574f648fc7fcab1c8123ef
Source dataset
uspto-grants-2005_05
Patent number
US06900200B2

Reaction notes

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