Ammonia → 3-[4-(4-Methylpiperazin-1-yl)-phenyl]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carboxylic acid amide

HRID 1506007Notes

Reaction equation

HRID 1506007 reaction equation
[CH3:1][CH2:2][N:3]([CH:7]([CH3:9])C)[CH:4]([CH3:6])[CH3:5].CN1CCN(C2C=[CH:21][C:20]([C:23]3[CH:38]=[N:37][C:26]4[NH:27][C:28]5[CH:33]=[N:32][C:31]([C:34](O)=[O:35])=[CH:30][C:29]=5[C:25]=4[CH:24]=3)=[CH:19]C=2)CC1.C1C[N:42]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)[CH2:41]C1.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=[N:78]C=2C=1.N.O1CCOCC1.S(=O)(=O)(O)O>CN(C=O)C.CS(C)=O>[CH3:41][N:42]1[CH2:1][CH2:2][N:3]([C:4]2[CH:5]=[CH:21][C:20]([C:23]3[CH:38]=[N:37][C:26]4[NH:27][C:28]5[CH:33]=[N:32][C:31]([C:34]([NH2:78])=[O:35])=[CH:30][C:29]=5[C:25]=4[CH:24]=3)=[CH:19][CH:6]=2)[CH2:7][CH2:9]1

Participants

10

Reactant 7

HCID 222AmmoniaHCID 1118Sulfuric AcidHCID 312751,4-DioxaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 582665593-[4-(4-Methylpiperazin-1-Yl)phenyl]-9h-Pyrrolo[2,3-B:5,4-C']dipyridine-6-Carboxylic Acid

Product 1

HCID 582664373-[4-(4-Methylpiperazin-1-yl)-phenyl]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (14 μL, 77 μmol) was added to a solution of 3-[4-(4-methylpiperazin-1-yl)-phenyl]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carboxylic acid (20.0 mg, 51.6 μmol), PyBOP (28.2 mg, 54.2 μmol) and HOBt (8.4 mg, 62 μmol) in DMF (1 mL). After 10 min at ambient temperature, a solution of 0.5M ammonia in 1,4-dioxane (500 μL, 0.258 mmol) was added to the reaction mixture. After 30 min the reaction mixture was acidified with 10% aqueous sulfuric acid and made homogeneous with the addition of DMSO. The crude solution was purified by preparative HPLC (0-30% MeCN over 30 min, 35 mL/min) to afford the title compound. 1H NMR (DMSO-D6, 400 MHz): 12.48 (s, 1H), 9.11-8.89 (m, 4H), 7.77 (d, J=8.9 Hz, 2H), 7.18 (d, J=8.9 Hz, 2H), 3.97 (d, J=13.5 Hz, 2H), 3.55 (q, J=12.2 Hz, 2H), 3.20 (q, J=11.4 Hz, 2H), 3.03 (t, J=12.0 Hz, 2H), 2.89 (s, 3H). LCMS (Method D): RT=6.35 min, M+H+=387.

Workup

  1. customThe crude solution was purified by preparative HPLC (0-30% MeCN over 30 min, 35 mL/min)

Sources & evidence

ORD record
ord-46d7ecd5987d4344849a711ff1cc2e3a
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

Loading…