Triethylamine → N-(3-((3-((1H-pyrrolo[2,3-b]pyridin-4-yl)methyl)ureido)methyl)phenyl)-3-cyclopentylpropiolamide

HRID 706350Notes

Reaction equation

HRID 706350 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][C:9]([CH2:10][NH2:11])=[C:4]2[CH:3]=[CH:2]1.C(N(CC)CC)C.[C:19]([N:26]1[CH:30]=[CH:29]N=C1)(N1C=CN=C1)=[O:20].N[CH2:32][C:33]1[CH:34]=[C:35]([NH:39][C:40](=[O:48])[C:41]#[C:42][CH:43]2[CH2:47][CH2:46][CH2:45][CH2:44]2)[CH:36]=CC=1>O1CCCC1>[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][C:9]([CH2:10][NH:11][C:19](=[O:20])[NH:26][CH2:30][C:29]3[CH:36]=[C:35]([NH:39][C:40](=[O:48])[C:41]#[C:42][CH:43]4[CH2:47][CH2:46][CH2:45][CH2:44]4)[CH:34]=[CH:33][CH:32]=3)=[C:4]2[CH:3]=[CH:2]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 11679841(1H-Pyrrolo[2,3-b]pyridin-4-yl)methanamineHCID 89525232N-(3-(aminomethyl)phenyl)-3-cyclopentylpropiolamide

Product 1

HCID 89525146N-(3-((3-((1H-pyrrolo[2,3-b]pyridin-4-yl)methyl)ureido)methyl)phenyl)-3-cyclopentylpropiolamideYield 33.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1H-pyrrolo[2,3-b]pyridin-4-yl)methanamine (198 mg, 1.345 mmol) in tetrahydrofuran (6 mL) were added triethylamine (0.563 mL, 4.04 mmol) and carbonyldiimidazole (327 mg, 2.018 mmol), and the mixture was stirred at room temperature for 18 h. N-(3-(aminomethyl)phenyl)-3-cyclopentylpropiolamide (326 mg, 1.345 mmol) was added and the mixture was stirred at room temperature for 18 h. The mixture was quenched with water (10 mL) and extracted with EtOAc (3×). The extract was dried (Na2SO4) and concentrated. The residue was purified using reverse-phase HPLC. The fractions containing the product were combined and concentrated. The residue was washed with 10% NaHCO3 and dried under vacuum to give 185 mg of product (N24229-78-A1)) as a white solid. MS: (M+H)+=416.3 1H NMR (400 MHz, DMSO-d6) δ ppm 2.75-2.86 (m, 6H), 3.16-3.27 (m, 2H), 3.57 (t, J=6.44 Hz, 2H), 5.41 (s, 2H), 6.56 (dd, J=8.08, 1.77 Hz, 1H), 7.10 (d, J=1.77 Hz, 1H), 7.20-7.29 (m, 1H), 8.56 (s, 1H), 8.77 (s, 1H).

Workup

  1. stirringthe mixture was stirred at room temperature for 18 h
  2. customThe mixture was quenched with water (10 mL)
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe extract was dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified
  7. additionThe fractions containing the product
  8. concentrationconcentrated
  9. washThe residue was washed with 10% NaHCO3
  10. customdried under vacuum

Sources & evidence

ORD record
ord-d2e7791f6e2848d9997db70c82b2ff3e
Source dataset
uspto-grants-2015_11
Patent number
US09174984B2

Reaction notes

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