1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → {4-[3-(1H-indol-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-(4-methyl-piperazin-1-yl)-methanone

HRID 85050Notes

Reaction equation

HRID 85050 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)O1.CCN=C=NCCCN(C)C.[CH3:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.Br[C:38]1[CH:39]=[C:40]2[C:46]([C:47]3[CH:48]=[C:49]4[C:53](=[CH:54][CH:55]=3)[NH:52][CH:51]=[CH:50]4)=[CH:45][N:44](S(C3C=CC(C)=CC=3)(=O)=O)[C:41]2=[N:42][CH:43]=1>CN(C1C=CN=CC=1)C.CC#N.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH:52]1[C:53]2[C:49](=[CH:48][C:47]([C:46]3[C:40]4[C:41](=[N:42][CH:43]=[C:38]([C:9]5[CH:10]=[CH:11][C:12]([C:13]([N:34]6[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]6)=[O:15])=[CH:16][CH:17]=5)[CH:39]=4)[NH:44][CH:45]=3)=[CH:55][CH:54]=2)[CH:50]=[CH:51]1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 531671-MethylpiperazineHCID 27346214-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 667791765-bromo-3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 66779396{4-[3-(1H-indol-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-(4-methyl-piperazin-1-yl)-methanoneYield 28%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid (100 mg, 0.403 mmol), EDCI (97 mg, 0.504 mmol) and DMAP (catalytic amount) were combined in CH3CN, stirred for 10 min and treated with N-methylpiperazine (54 μl, 0.484 mmol). The mixture was stirred overnight at room temperature. An aliquot of 650 μl was taken, combined with Intermediate B (50 mg, 0.107 mmol) and dichlorobis(triphenylphosphine)palladium (II) (10 mg, 0.013 mmol) and heated to 150° C. in a microwave reactor for 20 min. The mixture was partitioned between water and DCM, the organic phase dried, evaporated and purified by silica gel chromatography using 0-6% MeOH:DCM. 13 mg (28%) of the title compound were obtained. 1H NMR (DMSO-d6, 300 MHz): δ 11.88 (d, J=1.5 Hz, 1H), 11.08 (s, 1H), 8.57 (d, J=2.1 Hz, 1H), 8.45 (d, J=1.8 Hz, 1H), 7.90 (s, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.77 (d, J=2.4 Hz, 1H), 7.47 (m, 4H), 7.34 (t, J=2.6 Hz, 1H), 6.47 (t, J=2.4 Hz, 1H), 3.58 (bs, 4H), 2.3 (bs, 4H), 2.18 (s, 3H).

Workup

  1. stirringThe mixture was stirred overnight at room temperature
  2. customThe mixture was partitioned between water and DCM
  3. customthe organic phase dried
  4. customevaporated
  5. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-bb9d8cfb5f5f4eb1bb0085e26c199270
Source dataset
uspto-grants-2014_09
Patent number
US08846909B2

Reaction notes

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