2-Pyridinemethanamine → 1-(5-(5-Phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)pyridin-3-yl)ethane-1,2-diol

HRID 593712Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:5]([C:18]2[CH:19]=[N:20][CH:21]=[C:22]([CH:24]3[CH2:28][O:27]C(C)(C)[O:25]3)[CH:23]=2)=[N:4][N:3]=1.[N:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH2:37][NH2:38]>C1(C)C=CC=CC=1.C(Cl)Cl>[C:12]1([C:10]2[CH:9]=[CH:8][CH:7]=[C:6]3[C:11]=2[C:2]([NH:38][CH2:37][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][N:31]=2)=[N:3][N:4]=[C:5]3[C:18]2[CH:23]=[C:22]([CH:24]([OH:25])[CH2:28][OH:27])[CH:21]=[N:20][CH:19]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-chloro-1-(5-(2,2-dimethyl-1,3-dioxolan-4-yl)pyridin-3-yl)-5-phenylphthalazine (1.00 g, 2.39 mmol) in toluene (5 mL) was added pyridin-2-ylmethanamine (5.00 mL, 48.5 mmol) the contents were heated at 100° C. for 12 h. The reaction mixture was diluted with DCM (200 mL) and washed with 1.5N HCl (2 ×20 mL). The organic extract was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting crude was purified by preparative HPLC (Condition 18 as described in general methods) to obtain 1-(5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)pyridin-3-yl)ethane-1,2-diol (55.0 mg, 5.11%) as a white solid. The racemic product (50 mg) was resolved into individual enantiomers by chiral SFC (Condition 29 as described in general methods).

Workup

washwashed with 1.5N HCl (2 ×20 mL)
extractionThe organic extract
dry with materialwas dried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe resulting crude was purified by preparative HPLC (Condition 18 as described in general methods)

Sources & evidence

ORD record: ord-8bff044100bd440986ae462af654f76a
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242966B2

Reaction notes

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