Water → HCID 66760636, compound

HRID 889190Notes

Reaction equation

HRID 889190 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([N:13]2[CH2:17][CH2:16][CH:15]([C:18]([OH:20])=O)[CH2:14]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].OC1C2N=NNC=2C=CC=1.[NH2:31][CH2:32][C:33]([N:35]([C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([CH2:44][O:45][C:46]2[C:54]3[N:53]=[C:52]([O:55][CH3:56])[N:51]([CH2:57][C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][N:59]=4)[C:50]=3[CH:49]=[CH:48][CH:47]=2)[C:38]=1[Cl:64])[CH3:36])=[O:34].O>CN(C=O)C>[Cl:64][C:38]1[C:39]([CH2:44][O:45][C:46]2[C:54]3[N:53]=[C:52]([O:55][CH3:56])[N:51]([CH2:57][C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][N:59]=4)[C:50]=3[CH:49]=[CH:48][CH:47]=2)=[C:40]([Cl:43])[CH:41]=[CH:42][C:37]=1[N:35]([CH3:36])[C:33](=[O:34])[CH2:32][NH:31][C:18]([CH:15]1[CH2:16][CH2:17][N:13]([CH:10]2[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]2)[CH2:14]1)=[O:20]

Participants

6

Reactant 4

HCID 962WaterHCID 53413967HCID 53413967, compoundHCID 667603852-amino-N-(2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)-N-methylacetamideHCID 178418300HCID 178418300, compound

Product 1

HCID 66760636HCID 66760636, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1′-(tert-butoxycarbonyl)-[1,3′-bipyrrolidine]-3-carboxylic acid (0.5 g, 1.0 mmol) in anhydrous DMF (20 ml) was treated with HOBT (Hydroxybenzotriazole) (0.21 g, 1.52 mmol), EDCI (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide), hydrochloride (0.24 g, 1.27 mmol) then 2-amino-N-(2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)-N-methylacetamide (0.50 g, 1.0 mmol) and the mixture was stirred at room temperature overnight. The reaction was treated with water (100 mL) and the resulting precipitate was filtered. The aqueous mixture was treated with aqueous saturated sodium bicarbonate (100 mL), extracted with ethyl acetate (200 mL×2). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to give a white solid, 0.62 g that was purified by chromatography (silica gel, dichloromethane and methanol gradient) to afford tert-butyl 3-((2-((2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)(methyl)amino)-2-oxoethyl)carbamoyl)-[1,3′-bipyrrolidine]-1′-carboxylate as a white solid, 0.41 g (53%), that was pure by LC/MS (+ESI) m/z 766 (M+).

Workup

  1. filtrationthe resulting precipitate was filtered
  2. additionThe aqueous mixture was treated with aqueous saturated sodium bicarbonate (100 mL)
  3. extractionextracted with ethyl acetate (200 mL×2)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto give a white solid, 0.62 g that
  8. customwas purified by chromatography (silica gel, dichloromethane and methanol gradient)

Sources & evidence

ORD record
ord-14df206c6b1f4c0dadbe6f65e82b50da
Source dataset
uspto-grants-2012_08
Patent number
US08252793B2

Reaction notes

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