Tert-Butylamine → HCID 67520205, compound

HRID 1926167Notes

Reaction equation

HRID 1926167 reaction equation
Cl.C([O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][N:16]1[C:24]2[C:23]([NH:25][C:26]3[CH:41]=[CH:40][C:29]([O:30][C:31]4[CH:39]=[CH:38][C:34]([C:35]([OH:37])=O)=[CH:33][CH:32]=4)=[C:28]([Cl:42])[CH:27]=3)=[N:22][CH:21]=[N:20][C:19]=2[CH:18]=[CH:17]1)(=O)C1C=CC=CC=1.[CH3:43][C:44]([NH2:47])([CH3:46])[CH3:45].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>O.CN(C)C=O.C(N(CC)CC)C>[ClH:42].[C:44]([NH:47][C:35](=[O:37])[C:34]1[CH:38]=[CH:39][C:31]([O:30][C:29]2[CH:40]=[CH:41][C:26]([NH:25][C:23]3[C:24]4[N:16]([CH2:15][CH2:14][O:13][CH2:12][CH2:11][OH:10])[CH:17]=[CH:18][C:19]=4[N:20]=[CH:21][N:22]=3)=[CH:27][C:28]=2[Cl:42])=[CH:32][CH:33]=1)([CH3:46])([CH3:45])[CH3:43]

Participants

8

Reactant 4

HCID 6385Tert-ButylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67521149HCID 67521149, compound

Product 1

HCID 67520205HCID 67520205, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 4-{4-[(5-{2-[2-(benzoyloxy)ethoxy]ethyl}-5H-pyrrolo[3,2-d]pyrimidin-4-yl)amino]-2-chlorophenoxy}benzoic acid hydrochloride (183 mg), 2-methylpropan-2-amine (0.038 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (69 mg), 1-hydroxybenzotriazole monohydrate (55 mg), triethylamine (0.050 mL) and N,N-dimethylformamide (3 mL) was stirred overnight at room temperature. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol:ethyl acetate=0:100→10:90). The object fraction was concentrated under reduced pressure. The residue was dissolved in a mixed solvent of methanol (5 mL) and tetrahydrofuran (1 mL), 1N aqueous sodium hydroxide solution (0.6 mL) was added and the mixture was stirred at room temperature for 3 days. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to basic silica gel column chromatography (eluent, methanol:ethyl acetate=0:100→10:90). The object fraction was concentrated under reduced pressure. The residue was dissolved in ethyl acetate-ethanol, and 1N hydrochloric acid/ethyl acetate solution (0.3 mL) was added. The solvent was evaporated under reduced pressure and the obtained residue was crystallized from ethanol-ethyl acetate to give the title compound (118 mg) as a white powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. concentrationThe object fraction was concentrated under reduced pressure
  6. dissolutionThe residue was dissolved in a mixed solvent of methanol (5 mL) and tetrahydrofuran (1 mL), 1N aqueous sodium hydroxide solution (0.6 mL)
  7. additionwas added
  8. stirringthe mixture was stirred at room temperature for 3 days
  9. additionWater was added to the reaction mixture
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe ethyl acetate layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. concentrationThe object fraction was concentrated under reduced pressure
  15. dissolutionThe residue was dissolved in ethyl acetate-ethanol
  16. addition1N hydrochloric acid/ethyl acetate solution (0.3 mL) was added
  17. customThe solvent was evaporated under reduced pressure
  18. customthe obtained residue was crystallized from ethanol-ethyl acetate

Sources & evidence

ORD record
ord-d970eb50204f40cd988f217335461ba5
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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