Diisopropylethylamine → N-(3-(methylsulfonamido)phenyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinamide

HRID 593718Notes

Reaction equation

HRID 593718 reaction equation
[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[N:10][N:11]=[C:12]3[C:17]2[CH:18]=[N:19][CH:20]=[C:21]([CH:25]=2)[C:22]([OH:24])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:34][C:35]1[CH:36]=[C:37]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])[CH:38]=[CH:39][CH:40]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:45][S:42]([NH:41][C:37]1[CH:36]=[C:35]([NH:34][C:22](=[O:24])[C:21]2[CH:25]=[C:17]([C:12]3[C:13]4[C:8](=[C:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)[CH:16]=[CH:15][CH:14]=4)[C:9]([NH:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)=[N:10][N:11]=3)[CH:18]=[N:19][CH:20]=2)[CH:40]=[CH:39][CH:38]=1)(=[O:44])=[O:43]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2734262N-(3-Aminophenyl)methanesulfamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 904238795-(5-Phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinic acid

Product 1

HCID 86267256N-(3-(methylsulfonamido)phenyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinamideYield 27.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-(5-Phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinic acid (15.0 mg, 0.0350 mmol) was added to N-(3-aminophenyl)methanesulfonamide (7.73 mg, 0.0420 mmol) and a solution of HATU (19.7 mg, 0.0520 mmol) and DIPEA (0.0180 mL, 0.104 mmol) in DMF (0.5 mL) was added. The reaction mixture was stirred for 5 hours at room temperature. The volatile components were removed under high vacuum and the residue was purified by reverse phase preparative HPLC (Condition 36 as described in general methods) to afford N-(3-(methylsulfonamido)phenyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinamide (5.79 mg, 26.4%) as a white solid. LCMS (Condition 37): retention time 1.63 min, [M+1]=602.1, purity 95.02%. 1H NMR (400 MHz, DMSO-d6) δ 3.01 (s, 3 H), 4.67 (d, J=4.4 Hz, 2 H), 6.34 (t, J=4.4 Hz, 1 H), 6.95-6.99 (m, 1 H), 7.21-7.24 (m, 1 H), 7.28 (d, J=8.0 Hz, 1 H), 7.30 (t, J=8.0 Hz, 1 H), 7.50-7.58 (m, 6 H), 7.68-7.77 (m, 3 H), 7.90-7.94 (m, 2 H), 8.22-8.24 (m, 1 H), 8.61 (t, J=2.0 Hz, 1 H), 9.05 (d, J=2.0 Hz, 1 H), 9.26 (d, J=2.0 Hz, 1 H), 10.60 (s, 1 H).

Workup

  1. customThe volatile components were removed under high vacuum
  2. customthe residue was purified by reverse phase preparative HPLC (Condition 36 as described in general methods)

Sources & evidence

ORD record
ord-56f2c5342c734338a630fd683ecd1479
Source dataset
uspto-grants-2016_01
Patent number
US09242966B2

Reaction notes

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