Trifluoroacetic acid → 4-(azepan-1-yl)-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine

HRID 1042807Notes

Reaction equation

HRID 1042807 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([O:13][C:14]3[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=3)=[CH:8][CH:9]=[N:10]2)=[N:5][CH:4]=1.[N:21]1([C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31](Cl)=[N:30][N:29]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.C(O)(C(F)(F)F)=O>CCOC(C)=O>[N:21]1([C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31]([NH:20][C:17]3[CH:18]=[CH:19][C:14]([O:13][C:7]4[C:6]5[C:11](=[CH:12][C:3]([O:2][CH3:1])=[CH:4][N:5]=5)[N:10]=[CH:9][CH:8]=4)=[CH:15][CH:16]=3)=[N:30][N:29]=2)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 441851064-(7-Methoxy-1,5-naphthyridin-4-yloxy)benzenamineHCID 507435191-(Azepan-1-yl)-4-chlorophthalazine

Product 1

HCID 594273504-(azepan-1-yl)-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A pyrex reaction tube was charged with 4-(7-methoxy-1,5-naphthyridin-4-yloxy)benzenamine (128 mg, 0.478 mmol), 1-(azepan-1-yl)-4-chlorophthalazine (125 mg, 0.478 mmol), TFA (0.029 ml, 0.382 mmol) and 2.4 mL of 2-BuOH. The tube was sealed and the reaction mixture was heated at 100° C. for 1.5 h. Upon cooling, EtOAc was added, and the resulting precipitate was filtered and washed with EtOAc. The solid was dissolved in 90/10/1 CH2Cl2/MeOH/NH4OH and purified by silica gel chromatography with 90/10/1 CH2Cl2/MeOH/NH4OH. The material was further purified by reverse phase chromatography (Gilson, 5-95% ACN over 15 min) to provide 4-(azepan-1-yl)-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine as a tan solid. MS m/z=493 [M+H]+. Calc'd for C29H28N6O2: 492.57.

Workup

  1. customThe tube was sealed
  2. temperatureUpon cooling
  3. filtrationthe resulting precipitate was filtered
  4. washwashed with EtOAc
  5. dissolutionThe solid was dissolved in 90/10/1 CH2Cl2/MeOH/NH4OH
  6. custompurified by silica gel chromatography with 90/10/1 CH2Cl2/MeOH/NH4OH
  7. customThe material was further purified by reverse phase chromatography (Gilson, 5-95% ACN over 15 min)

Sources & evidence

ORD record
ord-01ff7bfbc4a84bc4b17d8939c7f3c0e4
Source dataset
uspto-grants-2013_10
Patent number
US08557816B2

Reaction notes

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