Pyridine → HCID 86270487, compound

HRID 593715Notes

Reaction equation

HRID 593715 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH:14]=[CH:15][CH:16]=3)[C:11]([NH:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[N:10][N:9]=2)[CH:5]=[N:6][CH:7]=1.N1C=CC=CC=1.[C:38](Cl)(=[O:43])[O:39][CH:40]([CH3:42])[CH3:41]>ClCCl>[C:18]1([C:13]2[CH:14]=[CH:15][CH:16]=[C:17]3[C:12]=2[C:11]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)=[N:10][N:9]=[C:8]3[C:4]2[CH:3]=[C:2]([NH:1][C:38](=[O:43])[O:39][CH:40]([CH3:42])[CH3:41])[CH:7]=[N:6][CH:5]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 7917Isopropyl chloroformateHCID 86270484HCID 86270484, compound

Product 1

HCID 86270487HCID 86270487, compoundYield 57.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(5-aminopyridin-3-yl)-8-phenyl-N-(pyridin-2-ylmethyl) phthalazin-1-amine (50.0 mg, 0.124 mmol) in dichloromethane (5 mL) at room temperature was added pyridine (0.0200 mL, 0.247 mmol) followed by isopropyl carbonochloridate (18.2 mg, 0.148 mmol). The reaction mixture was stirred at ambient temperature for 12 h then diluted with dichloromethane (50 mL) and the organic portion washed with water (10 mL) followed by brine (10 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC (Condition 32 as described in general methods) to afford isopropyl (5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)pyridin-3-yl)carbamate (35.0 mg, 57.7%). LCMS (Condition 4): retention time 2.16 min, [M+1]=491.0. HPLC (Condition 28): retention time=6.66 min, purity 95.13%. 1H NMR (400 MHz, DMSO-d6) δ 1.29 (d, J=6.0 Hz, 6 H), 4.65 (d, J=4.0 Hz, 2 H), 4.93 (sept, J=6.0 Hz, 1 H), 6.28 (t, J=4.0 Hz, 1 H), 7.22 (dd, J=6.0 Hz, J=7.6 Hz, 1 H), 7.28 (d, J=8.0 Hz, 1 H), 7.45-7.60 (m, 5 H), 7.68-7.73 (m, 2 H), 7.84-7.93 (m, 2 H), 8.17 (t, J=2.0 Hz, 1 H), 8.22-8.24 (m, 1 H), 8.48 (d, J=2.0 Hz, 1 H), 8.81 (d, J=2.0 Hz, 1 H), 10.00 (s, 1 H).

Workup

  1. washthe organic portion washed with water (10 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 preparative HPLC (Condition 32 as described in general methods)

Sources & evidence

ORD record
ord-34893a7f96a5403f9a834b55230877b9
Source dataset
uspto-grants-2016_01
Patent number
US09242966B2

Reaction notes

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