Triethylamine → HCID 86605389, compound

HRID 1180424Notes

Reaction equation

HRID 1180424 reaction equation
[CH3:1][CH:2]([CH3:30])[CH2:3][C@H:4]([O:9][C@@H:10]([C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH2:24]N(C)[CH2:26][CH2:27][CH:28]=2)=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5](OC)=[O:6].Cl.[NH2:32][CH2:33][C:34]#[N:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N([CH2:65][CH3:66])CC)C>[OH-].[K+].[Cl-].[Na+].O.CN(C=O)C.CO.C1COCC1>[C:34]([CH2:33][NH:32][C:5](=[O:6])[C@@H:4]([O:9][C@@H:10]([C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH2:24][CH:65]([CH3:66])[CH2:26][CH2:27][CH:28]=2)=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:3][CH:2]([CH3:1])[CH3:30])#[N:35]

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11491918Aminoacetonitrile hydrochlorideHCID 86605388HCID 86605388, compound

Product 1

HCID 86605389HCID 86605389, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 14797Potassium HydroxideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of methyl (2S)-4-methyl-2-{[(R)-[4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)phenyl](phenyl)methyl]oxy}pentanoate from example 36 step 4 (100 mg, 0.25 mmol), THF (1.5 mL), methanol (0.5 mL) and IN KOH (0.5 mL) was heated at 70° C. for 45 min. The mixture was concentrated and then 2 times with toluene to dry. To the residue was added DMF (1.5 mL), aminoacetonitrile hydrochloride (23 mg, 0.25 mmol), HATU coupling reagent (95 mg, 0.25 mmol) and triethylamine (75 mg, 0.75 mmol). The reagents were stirred at r.t. for 2 h, then added to dilute brine (5 mL) and extracted with 1:1 THF/ethyl acetate (25 mL). The organic layer was washed with brine (2×10 mL), dried (Na2SO4), filtered, concentrated and the residue purified by chromatography on silica gel using 10% methanol in dichloromethane to obtain the title compound as a white solid.

Workup

  1. concentrationThe mixture was concentrated
  2. dry with material2 times with toluene to dry
  3. extractionextracted with 1:1 THF/ethyl acetate (25 mL)
  4. washThe organic layer was washed with brine (2×10 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue purified by chromatography on silica gel using 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-88e90e6d64a24ddb89010a1c6403bded
Source dataset
uspto-grants-2007_10
Patent number
US07279478B2

Reaction notes

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