Morpholine → HCID 178423456, compound

HRID 77094Notes

Reaction equation

HRID 77094 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][CH:10]([C:13](O)=[O:14])[CH2:9]2)=[CH:4][C:3]=1[C:16]1[NH:20][C:19]2[CH:21]=[CH:22][C:23]([CH3:25])=[CH:24][C:18]=2[N:17]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][CH:10]([C:13]([N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)=[O:14])[CH2:9]2)=[CH:4][C:3]=1[C:16]1[NH:20][C:19]2[CH:21]=[CH:22][C:23]([CH3:25])=[CH:24][C:18]=2[N:17]=1

Participants

5

Reactant 4

HCID 8083MorpholineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178423458HCID 178423458, compound

Product 1

HCID 178423456HCID 178423456, compoundYield 47.1%

Conditions

Temperature
35 °C

Procedure

Method E—Step a To a vial with 1-[4-Chloro-3-(5-methyl-1H-benzoimidazol-2-yl)-phenyl]-pyrrolidine-3-carboxylic acid (obtained as described in general method 5, step b) (0.09 g, 0.25 mmol), HATU (0.10 g, 0.26 mmol), TEA (0.07 mL, 0.53 mmol) and morpholine (0.03 mL, 0.33 mmol) dichloromethane (2 mL) was added and the reaction mixture was heated at 35° C. overnight. Reaction was cooled to room temperature, saturated NaHCO3 solution (2 mL) was added with stirring, the organic layer recovered by filtration through phase separator, and the solvent removed under reduced pressure. The crude was purified by NH2 column (eluent: dichloromethane:MeOH from 10:0 to 5:5), and SCX to obtain 0.05 g of the title compound (46%).

Workup

  1. customReaction
  2. temperaturewas cooled to room temperature
  3. filtrationthe organic layer recovered by filtration through phase separator
  4. customthe solvent removed under reduced pressure
  5. customThe crude was purified by NH2 column (eluent: dichloromethane:MeOH from 10:0 to 5:5), and SCX

Sources & evidence

ORD record
ord-4c6e53e0d1e64181b78e60797239e02d
Source dataset
uspto-grants-2014_09
Patent number
US08835648B2

Reaction notes

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