Methanamine, hydrochloride (1:1) → HCID 67118574, compound

HRID 1189010Notes

Reaction equation

HRID 1189010 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([CH2:28][O:29][CH3:30])=[CH:26][CH:27]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18](O)=[O:19])[CH2:15][N:16]=1)=[CH:8]2.Cl.[CH2:32]([N:34]=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.[Cl-].C[NH3+]>CN(C)C=O.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([CH2:28][O:29][CH3:30])=[CH:26][CH:27]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([NH:34][CH3:32])=[O:19])[CH2:15][N:16]=1)=[CH:8]2

Participants

7

Reactant 4

HCID 11637Methanamine, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67118679HCID 67118679, compound

Product 1

HCID 67118574HCID 67118574, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of [2-(7-methoxy-5-{[6-(methoxymethyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (300 mg), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (270 mg), 1-hydroxybenzotriazole monohydrate (216 mg), methylammonium chloride (95 mg), triethylamine (0.2 mL) and N,N-dimethylformamide (13 mL) was stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure. The residue was dissolved in water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100 to 5/95, volume ratio), followed by silica gel column chromatography (methanol/ethyl acetate=0/100 to 8/92, volume ratio) to give a yellow oil. The oil was crystallized from acetonitrile-diethyl ether to give white crystals. The crystals were recrystallized from acetonitrile-diethyl ether to give the title compound (204 mg, 66%) as colorless crystals. MS 441 (MH+). mp 102-104° C.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in water
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100 to 5/95, volume ratio)
  9. customto give a yellow oil
  10. customThe oil was crystallized from acetonitrile-diethyl ether
  11. customto give white crystals
  12. customThe crystals were recrystallized from acetonitrile-diethyl ether

Sources & evidence

ORD record
ord-2c7e0b2361dc47f496b7877ab9e454f5
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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