Hydrochloric Acid → HCID 18470790, compound

HRID 2228741Notes

Reaction equation

HRID 2228741 reaction equation
C(O[C:9](=[O:38])[CH2:10][N:11]1[C:16](=[O:17])[C:15]([NH:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][N:28]([CH3:35])[C:29](=[O:34])[C:30]([F:33])([F:32])[F:31])[CH:22]=2)=[N:14][C:13](Cl)=[C:12]1[CH3:37])C1C=CC=CC=1.[CH3:39][C:40]1[C:48]2[C:43](=[CH:44][CH:45]=[C:46]([CH2:49][NH2:50])[CH:47]=2)[NH:42][CH:41]=1.C1C=CC2N(O)N=NC=2C=1.Cl.CN1CCOCC1>CO.[OH-].[OH-].[Pd+2].CN(C=O)C>[F:33][C:30]([F:31])([F:32])[C:29]([N:28]([CH3:35])[CH2:27][C:23]1[CH:24]=[CH:25][CH:26]=[C:21]([CH2:20][CH2:19][NH:18][C:15]2[C:16](=[O:17])[N:11]([CH2:10][C:9]([NH:50][CH2:49][C:46]3[CH:47]=[C:48]4[C:43](=[CH:44][CH:45]=3)[NH:42][CH:41]=[C:40]4[CH3:39])=[O:38])[C:12]([CH3:37])=[CH:13][N:14]=2)[CH:22]=1)=[O:34]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 18470813(3-methyl-1H-indol-5-yl)methanamineHCID 18470883HCID 18470883, compound

Product 1

HCID 18470790HCID 18470790, compoundYield 20.5%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Benzyl-2-[3-chloro-2-methyl-5-[(3{[methyl(2,2,2-trifluoroacetyl)amino]methyl}phenethyl)amino]-6-oxo-1(6H) pyrazinyl]acetate (preparation 37) (200 mg, 0.36 mmol) was dissolved in methanol (80 ml), treated with Pearlman's catalyst (80 mg) and stirred under a hydrogen atmosphere (60 psi, room temperature, 2.5 hr). The catalyst was removed by filtration, followed by evaporation of the solvent and azeotroping with CH2Cl2 to yield a crude solid. To the crude mixture, (3-methyl-1H-indol-5-yl)methylamine (preparation 36) (60 mg, 0.37 mmol), HOBT (56 mg, 0.41 mmol), WSCDI.HCl (91 mg, 0.47 mmol), N-methylmorpholine (0.073 ml, 0.66 mmol) and DMF (10 ml) were added and stirred at room temperature for 18 hr. The resultant mixture was evaporated to dryness and triturated with water. The brown solid was filtered, dried, then purified by chromatography (SiO2, gradient elution with 1:2 ethyl acetate:hexane; 2:1 ethyl acetate:hexane) to give the desired product (42 mg, 20%). 1H NMR (CD3OD) δ 2.15 (s, 3H), 2.30 (s, 3H), 2.85-3.20 (m, 3H), 3.35 (s, 2H), 3.60 (m, 2H), 4.50 (s, 2H), 4.604.65 (m, 2H), 4.75 (s, 2H), 6.65 (s, 1H), 6.95-7.50 (m, 8H). LRMS m/z=596.5 (M+1)+.

Workup

  1. customThe catalyst was removed by filtration
  2. customfollowed by evaporation of the solvent
  3. customazeotroping with CH2Cl2
  4. customto yield a crude solid
  5. stirringstirred at room temperature for 18 hr
  6. customThe resultant mixture was evaporated to dryness
  7. customtriturated with water
  8. filtrationThe brown solid was filtered
  9. customdried
  10. custompurified by chromatography (SiO2, gradient elution with 1:2 ethyl acetate:hexane; 2:1 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-4c5b7bf266394d9fbdfc87da34321990
Source dataset
uspto-grants-2002_07
Patent number
US06417203B1

Reaction notes

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