Aniline → HCID 59595044, compound

HRID 2263655Notes

Reaction equation

HRID 2263655 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:16][C:15]3[C:14](=[O:17])[N:13]([C:18]4[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26](O)(C)C)=[C:20]([O:30][CH3:31])[CH:19]=4)N=[N:11][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1([O:48]C(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.NC1C=CC=CC=1.C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.ClCCCl.O.C(Cl)Cl.CCOCC>[C:25]([O:24][C:21]1[CH:22]=[CH:23][C:18]([NH:13][C:14]([C:15]2[S:16][C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[CH:9][C:10]=2[NH2:11])=[O:17])=[CH:19][C:20]=1[O:30][CH3:31])(=[O:48])[CH3:26]

Participants

10

Reactant 5

HCID 6115AnilineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 25022526HCID 25022526, compound

Product 1

HCID 59595044HCID 59595044, compoundYield 69%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 21881112Ethyl ether methylene chlorideSolvent

Procedure

To a solution of 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylic acid prepared in Example 1, Part A (104 mg, 0.41 mmol) in NMP (1.8 mL) were added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (195 mg, 0.51 mmol) and N,N-diisopropylethylamine (0.22 mL, 1.26 mmol). After the resulting solution was stirred at RT for 2.3 h, a solution of the aniline prepared in Part B of Example 2 (84.3 mg, 0.465 mmol) in 1,2-dichloroethane (0.8 mL+0.4 mL rinse) was added. After heating at 80° C. with stirring for 16 h, the reaction was cooled to RT before being diluted first with water (30 mL) and then sat'd NaHCO3 (5.5 mL). Following extraction of the aqueous mixture (pH ˜9) with EtOAc (3×30 mL), the combined organic extracts were washed with water (20 mL), dried (Na2SO4) and evaporated. Chromatography (SiO2 230-400 mesh, 9/1 CH2Cl2/Ether) of the crude provided the desired amide (118.2 mg, 69% yield) as a yellow solid: MS (electrospray, + ions) m/z 417 (M+H).

Workup

  1. additionwas added
  2. temperatureAfter heating at 80° C.
  3. stirringwith stirring for 16 h
  4. temperaturethe reaction was cooled to RT
  5. extractionextraction of the aqueous mixture (pH ˜9) with EtOAc (3×30 mL)
  6. washthe combined organic extracts were washed with water (20 mL)
  7. dry with materialdried (Na2SO4)
  8. customevaporated

Sources & evidence

ORD record
ord-1c888c99123b4c2dbba603b1906a27bf
Source dataset
uspto-grants-2010_12
Patent number
US07851622B2

Reaction notes

Loading…