Diisopropylethylamine → 2-Bromo-N-(4-(2,6-dichlorobenzamido)pyridin-2-yl)thiazole-5-carboxamide

HRID 449867Notes

Reaction equation

HRID 449867 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.[Br:19][C:20]1[S:24][C:23]([C:25]([OH:27])=O)=[CH:22]C=1.C([N:31](C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O>[Br:19][C:20]1[S:24][C:23]([C:25]([NH:1][C:2]2[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]3[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=3[Cl:16])[CH:5]=[CH:4][N:3]=2)=[O:27])=[CH:22][N:31]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 3491155-Bromothiophene-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59618313N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide

Product 1

HCID 596184522-Bromo-N-(4-(2,6-dichlorobenzamido)pyridin-2-yl)thiazole-5-carboxamideYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide (282 mg, 1.00 mmol), 5-bromothiophene-2-carboxylic acid (624 mg, 3.0 mmol) in N,N-dimethylformamide (5 mL) was added diisopropylethylamine (700 μL, 4.00 mmol), followed by O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.14 g, 3.0 mmol). The mixture was heated at 60° C. for 24 hours. The mixture was then concentrated under reduced pressure and the residue was partitioned between EtOAc (30 mL) and 1 N NaOH (20 mL). The aqueous layer was extracted with EtOAc (2×30 mL). The combined organic extracts were dried over Na2SO4, and concentrated under reduced pressure. The redidue was purified by silica gel column chromatography (0-40% EtOAc/hexane) to afford the desired product as an-off-white solid (141 mg, 30% yield). 1H NMR (400 MHz, DMSO) δ 11.24 (s, 1H), 8.65 (s, 1H), 8.44 (d, J=1.6 Hz, 1H), 8.33 (d, J=5.7 Hz, 1H), 7.66-7.47 (m, 5H). LCMS (ESI) m/z: 472.7 [M+H+].

Workup

  1. concentrationThe mixture was then concentrated under reduced pressure
  2. customthe residue was partitioned between EtOAc (30 mL) and 1 N NaOH (20 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe redidue was purified by silica gel column chromatography (0-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-a9f44807b7264d67bcd1a4e7fea55a03
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Reaction notes

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