Trifluoroacetic acid → HCID 86694189, compound

HRID 707333Notes

Reaction equation

HRID 707333 reaction equation
C[O:2][C:3]1[N:11]([CH:12]2[CH2:15][N:14]([C:16]([O:18]C(C)(C)C)=O)[CH2:13]2)[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]=1.FC(F)(F)C(O)=O.N1CC(N2C3=NC=CC=C3NC2=O)C1.[NH:44]1[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=2[N:46]=[C:45]1C(O)=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>O.CN(C)C=O.ClCCl>[NH:44]1[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=2[N:46]=[C:45]1[C:16]([N:14]1[CH2:13][CH:12]([N:11]2[C:6]3=[N:7][CH:8]=[CH:9][CH:10]=[C:5]3[NH:4][C:3]2=[O:2])[CH2:15]1)=[O:18]

Participants

10

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 2332402-Benzimidazolecarboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 84014331HCID 84014331, compoundHCID 86694190HCID 86694190, compound2×

Product 1

HCID 86694189HCID 86694189, compoundYield 8.01%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl 3-(2-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)azetidine-1-carboxylate (intermediate 55, 450 mg, 1.479 mmol), trifluoroacetic acid (3.29 mL, 44.4 mmol) and dichloromethane (3 mL) was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and dried under high vacuum. The crude 3-(azetidin-3-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (250 mg, 0.598 mmol), 1H-benzimidazole-2-carboxylic acid (97 mg, 0.598 mmol), HBTU (227 mg, 0.598 mmol), triethylamine (0.416 mL, 2.99 mmol) and dry dimethylformamide (2 mL) were added to a 50 mL round bottom flask. The reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with saturated ammonium chloride and dried over magnesium sulfate before concentrating in vacuo to give the crude material as a tan solid. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g, hexane to ethyl acetate gradient) to provide 3-(1-(1H-benzo[d]imidazole-2-carbonyl)azetidin-3-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (16 mg, 0.048 mmol, 8.01% yield) as off-white solid. M+1=335.1 1H NMR (400 MHz, DMSO-d6) δ ppm 4.42 (t, J=9.29 Hz, 1 H) 4.66 (dd, J=10.27, 6.16 Hz, 1 H) 4.97-5.03 (m, 1 H) 5.21-5.36 (m, 2 H) 6.92 (dd, J=7.82, 5.28 Hz, 1 H) 7.12-7.18 (m, 1 H) 7.18-7.25 (m, 2 H) 7.44 (d, J=7.82 Hz, 1 H) 7.62 (d, J=8.22 Hz, 1 H) 7.84 (dd, J=5.28, 1.37 Hz, 1 H) 11.13 (br. s., 1 H) 13.16 (br. s., 1 H)

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customdried under high vacuum
  3. stirringThe reaction mixture was stirred at room temperature for 12 hours
  4. extractionextracted with ethyl acetate
  5. extractionThe organic extract
  6. washwas washed with saturated ammonium chloride
  7. dry with materialdried over magnesium sulfate
  8. concentrationbefore concentrating in vacuo
  9. customto give the crude material as a tan solid
  10. customThe crude material was absorbed onto a plug of silica gel
  11. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g, hexane to ethyl acetate gradient)

Sources & evidence

ORD record
ord-83a3837212654d198f3496a878bf4d5e
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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