1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 71618041, compound

HRID 875488Notes

Reaction equation

HRID 875488 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([Cl:28])[C:10]=1[C:11]([N:13]1[C:21]2[CH:20]=[CH:19][N:18]=[C:17]([NH:22][C:23]([CH:25]3[CH2:27][CH2:26]3)=[O:24])[C:16]=2[CH:15]=[CH:14]1)=[O:12])[C:5]([OH:7])=O.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH2:59][C@H:60]([C:62]([O:64][CH2:65][CH3:66])=[O:63])[CH3:61]>CN(C)C=O.O>[Cl:28][C:9]1[CH:8]=[C:4]([CH:3]=[C:2]([Cl:1])[C:10]=1[C:11]([N:13]1[C:21]2[CH:20]=[CH:19][N:18]=[C:17]([NH:22][C:23]([CH:25]3[CH2:26][CH2:27]3)=[O:24])[C:16]=2[CH:15]=[CH:14]1)=[O:12])[C:5]([NH:59][C@H:60]([C:62]([O:64][CH2:65][CH3:66])=[O:63])[CH3:61])=[O:7]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 76507L-Alanine ethyl esterHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 71061762HCID 71061762, compound

Product 1

HCID 71618041HCID 71618041, compoundYield 36.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 3,5-dichloro-4-({4-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[3,2-c]pyridin-1-yl}carbonyl)benzoic acid (100 mg, 0.23 mmol) in anhydrous dimethylformamide (5 mL) was treated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (68 mg, 0.358 mmol), 1-hydroxy-7-azabenzotriazole (37 mg, 0.276 mmol), N,N-diisopropylethylamine (89 mg, 0.69 mmol). Ethyl alaninate (38 mg, 0.25 mmol) was added and the reaction mixture was stirred at room temperature for about 16 hours. The reaction mixture was poured into water (100 mL) and extracted with ethylacetate (2×30 mL). The combined organic layer was washed with brine, dried over anhydrous sodium sulphate and concentrated to give crude product which was purified by flash silica gel column chromatography using linear gradient ethyl acetate and hexane to afford ethyl N-[3,5-dichloro-4-({4-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[3,2-c]pyridin-1-yl}carbonyl)benzoyl]alaninate (43 mg, 34%).

Workup

  1. extractionextracted with ethylacetate (2×30 mL)
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulphate
  4. concentrationconcentrated
  5. customto give crude product which
  6. customwas purified by flash silica gel column chromatography

Sources & evidence

ORD record
ord-c731e017dd464ad2b54debef8d998073
Source dataset
uspto-grants-2015_03
Patent number
US08980911B2

Reaction notes

Loading…