1-Hydroxybenzotriazole → HCID 67520614, compound

HRID 1925971Notes

Reaction equation

HRID 1925971 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[N:26]([CH2:27][C:28]4[CH:36]=[CH:35][C:31]([C:32]([OH:34])=O)=[CH:30][CH:29]=4)[CH:25]=[CH:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[CH3:37][C@H:38]1[CH2:43][NH:42][CH2:41][C@@H:40]([CH3:44])[NH:39]1.N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.O.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[N:26]([CH2:27][C:28]4[CH:29]=[CH:30][C:31]([C:32]([N:42]5[CH2:41][C@H:40]([CH3:44])[NH:39][C@H:38]([CH3:37])[CH2:43]5)=[O:34])=[CH:35][CH:36]=4)[CH:25]=[CH:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6950261rel-(2R,6S)-2,6-dimethylpiperazineHCID 57597378HCID 57597378, compound

Product 1

HCID 67520614HCID 67520614, compoundYield 59.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 4-{[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}benzoic acid (120 mg) in N,N-dimethylformamide (2.4 mL) were added cis-2,6-dimethylpiperazine (95 mg) and 1H-1,2,3-benzotriazol-1-ol (65 mg), and the mixture was stirred at room temperature for 15 min. N-[3-(Dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (92 mg) and triethylamine (0.2 mL) were added, and the mixture was stirred at room temperature for 12 hrs. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (25 mL×3). The organic layer was washed with saturated brine (20 mL×3) and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (basic silica gel, eluent:ethyl acetate/methanol=10/0→9/1). The object fraction was concentrated under reduced pressure. Chloroform/diisopropyl ether (3/7) was added to the residue and the resultant precipitate was collected by filtration and dried under reduced pressure to give the title compound (85 mg) as white powder crystals.

Workup

  1. stirringthe mixture was stirred at room temperature for 12 hrs
  2. extractionextracted with ethyl acetate (25 mL×3)
  3. washThe organic layer was washed with saturated brine (20 mL×3)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. concentrationThe object fraction was concentrated under reduced pressure
  7. additionChloroform/diisopropyl ether (3/7) was added to the residue
  8. filtrationthe resultant precipitate was collected by filtration
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-7927c20487ea4ddfbe36c89fc974a94c
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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