Diisopropylethylamine → 4-({7-[(3-fluoro-4-methoxybenzoyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)-N-methylpyridine-2-carboxamide

HRID 1640223Notes

Reaction equation

HRID 1640223 reaction equation
[NH2:1][CH:2]1[CH2:11][C:10]2[CH:9]=[C:8]([O:12][C:13]3[CH:18]=[CH:17][N:16]=[C:15]([C:19]([NH:21][CH3:22])=[O:20])[CH:14]=3)[CH:7]=[CH:6][C:5]=2[CH2:4][CH2:3]1.[F:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH3:34])[C:27](O)=[O:28].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CC(N(C)C)=O.CC(N(C)C)=O.CN1C(=O)CCC1.O>[F:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH3:34])[C:27]([NH:1][CH:2]1[CH2:11][C:10]2[CH:9]=[C:8]([O:12][C:13]3[CH:18]=[CH:17][N:16]=[C:15]([C:19]([NH:21][CH3:22])=[O:20])[CH:14]=3)[CH:7]=[CH:6][C:5]=2[CH2:4][CH2:3]1)=[O:28]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27334013-Fluoro-4-methoxybenzoic acidHCID 589024394-[(7-amino-5,6,7,8-tetrahydronaphthalen-2-yl)oxy]-N-methylpyridine-2-carboxamide

Product 1

HCID 589024604-({7-[(3-fluoro-4-methoxybenzoyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)-N-methylpyridine-2-carboxamideYield 70.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 31374DimethylacetamideSolventHCID 22717425N,N-dimethylacetamide 1-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 4-[(7-amino-5,6,7,8-tetrahydronaphthalen-2-yl)oxy]-N-methylpyridine-2-carboxamide (25 mg) in DMA (1 mL) were added 3-fluoro-4-methoxybenzoic acid (16 mg, 0.094 mmol), DIPEA (26 μL), and a solution of TBTU (41 mg, 0.128 mmol) in DMA:NMP (1:1 v/v, 1 mL). The reaction mixture was allowed to stir at rt for 24 h. Water was added and the mixture was extracted with DCM. The organic solution was concentrated and purified by reverse phase HPLC to give 4-({7-[(3-fluoro-4-methoxybenzoyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)-N-methylpyridine-2-carboxamide (26.5 mg, 70%). LCMS: (AA) ES+450.5.

Workup

  1. extractionthe mixture was extracted with DCM
  2. concentrationThe organic solution was concentrated
  3. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-bd9c7fa1a4ca48d8972d5e2531e847b6
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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