1-Hydroxybenzotriazole → HCID 10145683, compound

HRID 2184439Notes

Reaction equation

HRID 2184439 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:24]([OH:26])=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].[CH3:37][O:38][CH:39](N1CCNCC1)[CH3:40].O[N:48]1[C:52]2C=CC=C[C:51]=2[N:50]=N1.Cl.CN(C)[CH2:60][CH2:61]CN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[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:24]([N:50]4[CH2:51][CH2:52][N:48]([CH2:40][CH2:39][O:38][CH3:37])[CH2:61][CH2:60]4)=[O:26])=[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:35])([F:34])[F:36]

Participants

8

Reactant 5

HCID 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 acidHCID 21918887HCID 21918887, compound

Product 1

HCID 10145683HCID 10145683, compoundYield 50.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 10-[(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)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) and 1-methoxyethylpiperazine (0.18 mL, 1.25 mmol) in N,N-dimethylformamide (4 mL) was added 1-hydroxybenzotriazole (0.15 g, 1.11 mmol) and 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.22 g, 1.15 mmol) followed by N,N-diisopropylethyl amine (0.27 mL, 1.55 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 oil. Purification by flash chromatography using a solvent system of 5% methanol in chloroform gave a white foam which was crystallized from diethyl ether to provide 0.32 g of title product as a white solid, m.p. 140-144° C.

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 oil
  6. customPurification by flash chromatography
  7. customgave a white foam which
  8. customwas crystallized from diethyl ether

Sources & evidence

ORD record
ord-f55ab9bd0a7d41e6ae06ca7eac05e6cd
Source dataset
uspto-grants-2005_05
Patent number
US06900200B2

Reaction notes

Loading…