Diethylamine → N,N-diethyl-N'-[4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]urea

HRID 1727732Notes

Reaction equation

HRID 1727732 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:22]=[CH:21][C:20]([CH2:23][N:24]5[CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:19][CH:18]=4)=[CH:16][C:9]=23)[C:5]([C:29]2[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=2)=[N:4]1)[CH3:2].Cl[C:37](OC1C=CC([N+]([O-])=O)=CC=1)=[O:38].[CH2:49]([NH:51][CH2:52][CH3:53])[CH3:50]>C1COCC1>[CH2:49]([N:51]([CH2:52][CH3:53])[C:37]([NH:33][C:32]1[CH:31]=[CH:30][C:29]([C:5]2[C:6]([C:8]3[CH:13]=[CH:12][N:11]=[C:10]4[NH:14][C:15]([C:17]5[CH:18]=[CH:19][C:20]([CH2:23][N:24]6[CH2:28][CH2:27][CH2:26][CH2:25]6)=[CH:21][CH:22]=5)=[CH:16][C:9]=34)=[CH:7][N:3]([CH2:1][CH3:2])[N:4]=2)=[CH:35][CH:34]=1)=[O:38])[CH3:50]

Participants

5

Reactant 3

HCID 8021DiethylamineHCID 821294-Nitrophenyl chloroformateHCID 68995250HCID 68995250, compound

Product 1

HCID 24816135N,N-diethyl-N'-[4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]ureaYield 37.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cloudy mixture of 4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)aniline (350 mg, 0.76 mmol) in dry THF (8 mL) was added 4-nitrophenyl chloroformate (168 mg, 0.83 mmol). The resultant slurry was stirred at room temperature for 45 min and diethylamine (0.32 mL, 3.03 mmol) was added. After 1 h, the reaction was concentrated under reduced pressure and diluted with 1N NaOH and EtOAc. The aqueous layer was extracted with three portions of EtOAc followed by 5% MeOH in EtOAc and the combined extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA) to provide 159 mg (32%) of the title product as a bis-TFA salt (yellow solid). ESMS [M+H]+: 562.4

Workup

  1. waitAfter 1 h
  2. concentrationthe reaction was concentrated under reduced pressure
  3. additiondiluted with 1N NaOH and EtOAc
  4. extractionThe aqueous layer was extracted with three portions of EtOAc
  5. dry with materialthe combined extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA)

Sources & evidence

ORD record
ord-21362ebab2084030874f5b37ecef53ed
Source dataset
uspto-grants-2009_02
Patent number
US07495102B2

Reaction notes

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