Triethylamine → 2-(4-Cyano-phenyl)-N-{5-[7-(1-hydroxymethyl-cyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl]-pyridin-3-yl}-acetamide

HRID 82130

Reaction equation

HRID 82130 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1)#[N:2].[NH2:13][C:14]1[CH:15]=[C:16]([C:20]([C:22]2[C:30]3[CH:29]=[N:28][CH:27]=[N:26][C:25]=3[N:24]([C:31]3([CH2:34][O:35]C4CCCCO4)[CH2:33][CH2:32]3)[CH:23]=2)=[O:21])[CH:17]=[N:18][CH:19]=1.CCCP(O)(O)=O.C(N(CC)CC)C>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:9][C:10]([NH:13][C:14]2[CH:19]=[N:18][CH:17]=[C:16]([C:20]([C:22]3[C:30]4[CH:29]=[N:28][CH:27]=[N:26][C:25]=4[N:24]([C:31]4([CH2:34][OH:35])[CH2:33][CH2:32]4)[CH:23]=3)=[O:21])[CH:15]=2)=[O:12])=[CH:7][CH:8]=1)#[N:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 795874-Cyanophenylacetic acidHCID 204484Propylphosphonic acidHCID 70817578(5-Amino-pyridin-3-yl)-{7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanone

Product 1

HCID 708171802-(4-Cyano-phenyl)-N-{5-[7-(1-hydroxymethyl-cyclopropyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl]-pyridin-3-yl}-acetamideYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

(4-Cyano-phenyl)-acetic acid (6.1 mg, 0.04 mmol) was added to a solution of (5-Amino-pyridin-3-yl)-{7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanone (15 mg, 0.04 mmol) (Preparation 251) in THF (1 mL). Then 1-propylphosphonic acid cyclic anhydride (0.07 mL, 0.11 mmol) and triethylamine (0.02 mL, 0.13 mmol) were added and the mixture was stirred at 25° C. for 4 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (2 mL) and extracted with ethyl acetate (3×5 mL). The combined organic layer was washed with water (5 mL), brine (5 mL), dried over sodium sulphate and evaporated in vacuo. The crude was dissolved in methanol (1 mL), PTSA (5 mg) was added and stirred at room temperature for 16 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (2 mL) and extracted with dichloromethane (5×5 mL). The combined organic layer was washed with brine (5 mL), dried over sodium sulphate and evaporated in vacuo. The crude material was purified by preparative TLC (dichloromethane:methanol 95:5) to afford the title compound as a white solid in 58% yield, 10 mg.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (2 mL)
  2. extractionextracted with ethyl acetate (3×5 mL)
  3. washThe combined organic layer was washed with water (5 mL), brine (5 mL)
  4. dry with materialdried over sodium sulphate
  5. customevaporated in vacuo
  6. dissolutionThe crude was dissolved in methanol (1 mL)
  7. additionPTSA (5 mg) was added
  8. stirringstirred at room temperature for 16 hours
  9. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (2 mL)
  10. extractionextracted with dichloromethane (5×5 mL)
  11. washThe combined organic layer was washed with brine (5 mL)
  12. dry with materialdried over sodium sulphate
  13. customevaporated in vacuo
  14. customThe crude material was purified by preparative TLC (dichloromethane:methanol 95:5)

Sources & evidence

ORD record
ord-cff01c6468024258a775d136e338733e
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Linked notes

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