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

HRID 1888547Notes

Reaction equation

HRID 1888547 reaction equation
[CH3:1][CH2:2][N:3](C(C)C)C(C)C.[CH3:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[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]([OH:36])=O)=[CH:30][C:29]=5[C:25]=4[CH:24]=3)=[CH:19][CH:18]=2)[CH2:13][CH2:12]1.C1CN([P+]([O:55]N2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(CN)O.S(=O)(=O)(O)O>CN(C=O)C>[OH:55][CH2:1][CH2:2][NH:3][C:34]([C:31]1[N:32]=[CH:33][C:28]2[NH:27][C:26]3[N:37]=[CH:38][C:23]([C:20]4[CH:19]=[CH:18][C:17]([N:14]5[CH2:13][CH2:12][N:11]([CH3:10])[CH2:16][CH2:15]5)=[CH:22][CH:21]=4)=[CH:24][C:25]=3[C:29]=2[CH:30]=1)=[O:36]

Participants

8

Reactant 6

HCID 700EthanolamineHCID 1118Sulfuric AcidHCID 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 582664473-[4-(4-Methylpiperazin-1-yl)-phenyl]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carboxylic acid (2-hydroxy-ethyl)amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (13.5 μL, 77.4 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 (0.6 mL). After 10 min at ambient temperature, ethanolamine (16 μL, 0.26 mmol) was added to the reaction mixture. After 30 min the resultant mixture was acidified with 10% aqueous sulfuric acid and concentrated in vacuo. The resultant residue was dissolved in DMF, water and 10% aqueous sulfuric acid and purified by preparative HPLC (0-30% MeCN over 30 min, 35 mL/min) to afford the title compound. 1H NMR (DMSO-D6, 400 MHz): 12.49 (s, 1H), 9.71 (br.s, 1H), 9.14 (d, J=2.1 Hz, 1H), 8.90 (s, 1H), 8.94 (d, J=2.2 Hz, 1H), 8.66 (t, J=5.8 Hz, 1H), 7.77 (d, J=8.7 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 3.97 (d, J=13.4 Hz, 2H), 3.57 (m, 4H), 3.45 (m, 2H), 3.20 (m, 2H), 3.04 (m, 2H), 2.89 (s. 3H), LCMS (Method D): RT=6.31 min, M+H+=431.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in DMF
  3. customwater and 10% aqueous sulfuric acid and purified by preparative HPLC (0-30% MeCN over 30 min, 35 mL/min)

Sources & evidence

ORD record
ord-20711901995441eb9b9ac1a0e39ed260
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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