1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → US10493060, Example BVD-523

HRID 1479147Notes

Reaction equation

HRID 1479147 reaction equation
[Cl:1][C:2]1[C:3]([C:12]2[CH:13]=[C:14]([C:17]([OH:19])=O)[NH:15][CH:16]=2)=[CH:4][C:5]([NH:8][CH:9]([CH3:11])[CH3:10])=[N:6][CH:7]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH:41]1[CH:46]=[C:45]([Cl:47])[CH:44]=[C:43]([C@H:48]([NH2:51])[CH2:49][OH:50])[CH:42]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[Cl:47][C:45]1[CH:44]=[C:43]([CH:48]([NH:51][C:17]([C:14]2[NH:15][CH:16]=[C:12]([C:3]3[C:2]([Cl:1])=[CH:7][N:6]=[C:5]([NH:8][CH:9]([CH3:10])[CH3:11])[CH:4]=3)[CH:13]=2)=[O:19])[CH2:49][OH:50])[CH:42]=[CH:41][CH:46]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 586419264-(5-chloro-2-(isopropylamino)pyridin-4-yl)-1H-pyrrole-2-carboxylic acidHCID 59694427(S)-2-amino-2-(3-chlorophenyl)ethanol

Product 1

HCID 58641927US10493060, Example BVD-523Yield 64%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of 4-(5-chloro-2-isopropylaminopyridin-4-yl)-1H-pyrrole-2-carboxylic acid (1.93 g, 6.9 mmol, 1.0 equivalent) in DMF (5.0 mL) was added EDCI (1.45 g, 7.6 mmol, 1.1 equivalents), HOBt (0.94 g, 6.9 mmol, 1.0 equivalent) and (S)-3-chlorophenylglycynol (1.58 g, 7.6 mmol, 1.1 equivalents). Diisopropylethylamine (2.7 mL) was then added and the resulting mixture was stirred a room temperature overnight. The mixture was then poured into water and extracted with ethyl acetate. After drying over sodium sulfate, the solvent was removed and the crude was adsorbed on silica gel. Purification was effected by flash chromatography on silica, eluting with mixtures of hexanes/acetone (from 80:20 to 60:40) to afford the title compound as white solid (1.9 g, 64%). Rt(min) 4.981 s. FIA MS: 433.1 ES+; 431.2 ES−. 1HNMR (CD3OD) δ 1.31 (d, 6H), 3.85 (m, 3H), 5.15 (t, 1H), 7.01 (s, 1H), 7.25 (m, 3H), 7.4 (s, 1H), 7.45 (s, 1H), 7.7 (s, 1H), 7.95 (s, 1H).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialAfter drying over sodium sulfate
  3. customthe solvent was removed
  4. customPurification
  5. washeluting with mixtures of hexanes/acetone (from 80:20 to 60:40)

Sources & evidence

ORD record
ord-d15e9273037b40e196ef330a34eeda3c
Source dataset
uspto-grants-2016_08
Patent number
USRE046097E1

Reaction notes

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