4-Aminopyridine → HCID 58063505, compound

HRID 2035716Notes

Reaction equation

HRID 2035716 reaction equation
[F:1][C:2]1[C:7]2[CH2:8][CH2:9][CH:10]([N:19]3[CH:23]=[C:22]([C:24]4[CH:29]=[CH:28][C:27](I)=[C:26]([O:31][CH3:32])[CH:25]=4)[N:21]=[N:20]3)[C:11](=[O:18])[N:12]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:6]=2[CH:5]=[CH:4][CH:3]=1.C1OCCOCCOCCOCCOCCOC1.[N:51]1[CH:56]=[CH:55][C:54]([NH2:57])=[CH:53][CH:52]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]1[C:7]2[CH2:8][CH2:9][CH:10]([N:19]3[CH:23]=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([NH:57][C:54]5[CH:55]=[CH:56][N:51]=[CH:52][CH:53]=5)=[C:26]([O:31][CH3:32])[CH:25]=4)[N:21]=[N:20]3)[C:11](=[O:18])[N:12]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 17274-AminopyridineHCID 2855718-Crown-6HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 666829706-Fluoro-3-[4-(4-iodo-3-methoxy-phenyl)-1,2,3-triazol-1-yl]-1-(2,2,2-trifluoro-ethyl)-1,3,4,5-tetrahydro-1-benzazepin-2-one

Product 1

HCID 58063505HCID 58063505, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 6-fluoro-3-[4-(4-iodo-3-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (50 mg, 0.089 mmol), 18-CROWN-6 (28.3 mg, 0.107 mmol), pyridin-4-amine (9.24 mg, 0.098 mmol), BINAP (11.11 mg, 0.018 mmol), sodium tert-butoxide (17.15 mg, 0.178 mmol), and tris(dibenzylideneacetone)dipalladium (4.09 mg, 4.46 μmol) were combined in a microwave vial and dissolved in THF (892 μl). The reaction was irradiated in the microwave at 160° C. for 15 minutes. The reaction mixture was filtered, and the solvent was removed in vacuo. Analytically pure material was obtained by purification by preparative HPLC Reverse phase (C-18), eluting with acetonitrile/water+0.05% Formic Acid. Lyophilisation afforded 6-fluoro-3-{-4-[3-methoxy-4-(pyridin-4-ylamino)phenyl]-1H-1,2,3-triazol-1-yl}-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one.

Workup

  1. customThe reaction was irradiated in the microwave at 160° C. for 15 minutes
  2. filtrationThe reaction mixture was filtered
  3. customthe solvent was removed in vacuo
  4. customAnalytically pure material was obtained by purification by preparative HPLC Reverse phase (C-18)
  5. washeluting with acetonitrile/water+0.05% Formic Acid

Sources & evidence

ORD record
ord-6a29de4a22e04e7d855436f5f8989284
Source dataset
uspto-grants-2013_11
Patent number
US08575150B2

Reaction notes

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