HCID 57677677, compound → HCID 86602167, compound

HRID 492849Notes

Reaction equation

HRID 492849 reaction equation
[CH3:1][N:2]([CH3:37])[CH:3]1[CH2:8][CH2:7][N:6]([C:9]([NH:11][C:12]2[CH:17]=[C:16]([O:18][C:19]3[CH:24]=[CH:23][C:22]([NH:25]C(=O)OCC4C=CC=CC=4)=[C:21]([F:36])[CH:20]=3)[CH:15]=[CH:14][N:13]=2)=[O:10])[CH2:5][CH2:4]1>O1CCCC1.[C].[Pd]>[NH2:25][C:22]1[CH:23]=[CH:24][C:19]([O:18][C:16]2[CH:15]=[CH:14][N:13]=[C:12]([NH:11][C:9]([N:6]3[CH2:5][CH2:4][CH:3]([N:2]([CH3:1])[CH3:37])[CH2:8][CH2:7]3)=[O:10])[CH:17]=2)=[CH:20][C:21]=1[F:36]

Participants

4

Reactant 1

HCID 57677677HCID 57677677, compound

Product 1

HCID 86602167HCID 86602167, compound

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

After adding 10% palladium-carbon (21.2 mg) to a solution of benzyl (4-{2-[(4-dimethylaminopiperidine-1-carbonyl)amino]pyridin-4-yloxy}-2-fluorophenyl)carbamate (101 mg) in tetrahydrofuran (10 ml), the mixture was stirred for 16 hours at room temperature under a hydrogen atmosphere. The catalyst was filtered and washed with tetrahydrofuran (4 ml) to provide a solution of 4-dimethylaminopiperidine-1-carboxylic acid [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]amide in tetrahydrofuran (14 ml). A 7 ml portion thereof was concentrated to almost dryness. A solution of 2-phenylacetyl isothiocyanate (26.4 mg) in toluene (3.0 ml) was added to a solution of the residue in ethanol (3.0 ml) at room temperature, and the mixture was stirred for 2 hours at room temperature. The reaction mixture was partitioned between ethyl acetate (60 ml) and saturated aqueous sodium hydrogencarbonate (30 ml). The organic layer was washed with brine and dried over anhydrous sodium sulfate. The organic layer was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol 20:1). The obtained solid was suspended in hexane and filtered. It was then washed with hexane. It was subsequently purified by LC-MS (eluent; acetonitrile-water-trifluoroacetic acid system). Fractions containing the target compound were concentrated, and then the residue was partitioned between saturated aqueous sodium hydrogencarbonate and ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. The organic layer was then concentrated to provide the title compound (8.4 mg) as white powder.

Workup

  1. filtrationThe catalyst was filtered
  2. washwashed with tetrahydrofuran (4 ml)

Sources & evidence

ORD record
ord-a63c8a7beb1b4c8c948a26a23452d4f2
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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