Triethylamine → 1H-Pyrrolo[3,2-b]pyridine-3-carboxamide, N-(2-fluoroethyl)-1-[(6-methoxy-5-methyl-4-pyrimidinyl)methyl]-

HRID 1753229Notes

Reaction equation

HRID 1753229 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]([OH:21])=O)=[CH:11]2)[C:4]=1[CH3:22].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.Cl.[F:49][CH2:50][CH2:51][NH2:52]>C(Cl)Cl.O>[F:49][CH2:50][CH2:51][NH:52][C:19]([C:12]1[C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:18]2[N:10]([CH2:9][C:5]2[C:4]([CH3:22])=[C:3]([O:2][CH3:1])[N:8]=[CH:7][N:6]=2)[CH:11]=1)=[O:21]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9995Ethanamine, 2-fluoro-, hydrochlorideHCID 111923Propylphosphonic anhydrideHCID 1178190601-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid

Product 1

HCID 727926311H-Pyrrolo[3,2-b]pyridine-3-carboxamide, N-(2-fluoroethyl)-1-[(6-methoxy-5-methyl-4-pyrimidinyl)methyl]-Yield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

See FIG. 16(c). 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid (250 mg, 0.84 mmol) was taken in a 100 ml single necked flask equipped with an air condenser connected to nitrogen source. DCM (10 mL) was added to get a suspension. Triethyl amine (1.162 mL, 8.38 mmol) was added to get a clear solution. 1-Propanephosphonic acid cyclic anhydride (1.497 mL, 2.51 mmol) was added followed by the addition of 2-fluoroethanamine hydrochloride (83 mg, 0.84 mmol). The reaction mass was stirred at RT for overnight, suspension was observed. After completion of the reaction, diluted with DCM, added water, and separated the DCM layer washed with brine solution. The DCM layer was dried over sodium sulphate, evaporated and purified the compound by column chromatography. Yield-52%. ES+MS m/z: 344 (M+1). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.25 (s, 20 H) 3.67 (d, J=5.46 Hz, 7 H) 3.77 (d, J=5.46 Hz, 7 H) 4.50 (t, J=4.90 Hz, 7 H) 4.66 (t, J=4.99 Hz, 7 H) 5.69 (s, 13 H) 7.26 (dd, J=8.29, 4.71 Hz, 7 H) 7.94 (d, J=8.48 Hz, 7 H) 8.28 (s, 7 H) 8.41 (s, 6 H) 8.49 (d, J=4.52 Hz, 7 H) 8.95 (t, J=5.84 Hz, 7 H).

Workup

  1. customequipped with an air condenser
  2. customto get a suspension
  3. customto get a clear solution
  4. customAfter completion of the reaction
  5. customseparated the DCM layer
  6. washwashed with brine solution
  7. dry with materialThe DCM layer was dried over sodium sulphate
  8. customevaporated
  9. custompurified the compound by column chromatography

Sources & evidence

ORD record
ord-00245a89c1bf4f06870f0606b6f66219
Source dataset
uspto-grants-2015_10
Patent number
US09163020B2

Reaction notes

Loading…