Benzylamine → N-benzyl-4-(2-(tert-butoxy)pyridin-4-yl)-8-phenylphthalazin-1-amine

HRID 593717Notes

Reaction equation

HRID 593717 reaction equation
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([O:13][C:14]1[CH:19]=[C:18]([C:20]2[C:29]3[C:24](=[C:25]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH:26]=[CH:27][CH:28]=3)[C:23](Cl)=[N:22][N:21]=2)[CH:17]=[CH:16][N:15]=1)([CH3:12])([CH3:11])[CH3:10]>ClCCl>[CH2:1]([NH:8][C:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:20]([C:18]2[CH:17]=[CH:16][N:15]=[C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])[CH:19]=2)=[N:21][N:22]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 7504BenzylamineHCID 904241491-(2-(Tert-butoxy)pyridin-4-yl)-4-chloro-5-phenylphthalazine

Product 1

HCID 90435497N-benzyl-4-(2-(tert-butoxy)pyridin-4-yl)-8-phenylphthalazin-1-amineYield 50.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Benzylamine (5.00 mL, 45.8 mmol) was added to 1-(2-(tert-butoxy)pyridin-4-yl)-4-chloro-5-phenylphthalazine (0.200 g, 0.513 mmol) and heated in a sealed tube at 100° C. for 12 h. The reaction mixture was diluted with dichloromethane (100 mL) and washed with water (50 mL) followed by brine (25 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography using Combiflash Isco (REDISEP®, basic Al2O3, 80 g, 0-70% ethyl acetate/petroleum ether) to remove excess benzyl amine. The resulting residue was then purified by preparative HPLC (Condition 33 as described in general methods) to afford N-benzyl-4-(2-(tert-butoxy)pyridin-4-yl)-8-phenylphthalazin-1-amine (0.120 g, 50.8%) as a white solid. LCMS (Condition 34): retention time 2.67 min, [M+1]=461.2. HPLC (Condition 35): retention time=21.80 min, purity 99.30%. 1H NMR (400 MHz, DMSO-d6) δ 1.63 (s, 9 H), 4.50 (d, J=5.2 Hz, 2 H), 5.07 (t, J=5.2 Hz, 1 H), 6.90 (dd, J=0.4 Hz, J=0.8 Hz, 1 H), 7.00-7.03 (m, 2 H), 7.17 (dd, J=1.6 Hz, J=5.2 Hz, 1 H), 7.22-7.28 (m, 3 H), 7.42-7.50 (m, 5 H), 7.67 (dd, J=1.2 Hz, J=6.8 Hz, 1 H), 7.85-7.93 (m, 2 H), 8.31 (dd, J=0.4 Hz, J=5.2 Hz, 1 H).

Workup

  1. washwashed with water (50 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by flash chromatography
  6. customto remove excess benzyl amine
  7. customThe resulting residue was then purified by preparative HPLC (Condition 33 as described in general methods)

Sources & evidence

ORD record
ord-8d8fba6a6ad8404ead63506885a86d7a
Source dataset
uspto-grants-2016_01
Patent number
US09242966B2

Reaction notes

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