Ammonium Chloride → 6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-cyclopropyl-phenyl)-amide

HRID 1094507Notes

Reaction equation

HRID 1094507 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=2)[NH2:7])[CH2:3][CH2:2]1.C[Al](C)C.C[O:16][C:17]([C:19]1[C:28]2[C:23](=[CH:24][C:25]([O:29][C:30]3[CH:35]=[CH:34][N:33]=[C:32]([CH2:36][O:37][CH3:38])[N:31]=3)=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1)=O.[NH4+].[Cl-]>C1(C)C=CC=CC=1.C1COCC1.CCOC(C)=O.O>[CH:1]1([C:4]2[CH:5]=[C:6]([NH:7][C:17]([C:19]3[C:28]4[C:23](=[CH:24][C:25]([O:29][C:30]5[CH:35]=[CH:34][N:33]=[C:32]([CH2:36][O:37][CH3:38])[N:31]=5)=[CH:26][CH:27]=4)[CH:22]=[CH:21][CH:20]=3)=[O:16])[CH:8]=[CH:9][CH:10]=2)[CH2:3][CH2:2]1

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 120321393-CyclopropylanilineHCID 16682925TrimethylaluminumHCID 591759856-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid methyl ester

Product 1

HCID 236528666-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-cyclopropyl-phenyl)-amide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

In a dried vessel, 32.8 mg (0.247 mMol) 3-cyclopropyl-aniline [preparation see: Tet. Lett. 43 (2002) 6987] are dissolved in 4.3 ml toluene and cooled to 10° C. Then 370 μl Me3Al (2 M in toluene; 0.74 mMol) are added via syringe. After 1 h at rt, a solution of 80 mg (0.247 mMol) 6-(2-methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid methyl ester (Step 15.4) in 1 ml THF is added and the reaction mixture is stirred for 30 min in an oil bath of 110° C. The solution is cooled in ice and hydrolyzed with 11 ml of a sat. NH4Cl. After 15 min stirring, the mixture is diluted with EtOAc and water, the aq. phase separated off and extracted with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Chromatography (Combi Flash; toluene/acetone 99:1→4:1) gives the title compound: MS: [M+1]+=426; TLC (toluene/acetone 4:1): Rf=0.09.

Workup

  1. stirringAfter 15 min stirring
  2. customthe aq. phase separated off
  3. extractionextracted with EtOAc
  4. washThe organic layers are washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ef89e87ade3f4b2b8f84421b0ac5f646
Source dataset
uspto-grants-2012_03
Patent number
US08133886B2

Reaction notes

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