Potassium Carbonate → 5-Methyl-thiazole-2-carboxylic acid (3-[methyl-(3-styryl-1H-indazol-6-yl)-amino]-phenyl]-amide

HRID 2181518Notes

Reaction equation

HRID 2181518 reaction equation
[CH3:1][N:2]([C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH:19]=[CH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:15][NH:16]2)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH2:9])[CH:4]=1.[CH3:27][C:28]1[S:32][C:31]([C:33](O)=[O:34])=[N:30][CH:29]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O.C(Cl)Cl.CCOC(C)=O>[CH3:1][N:2]([C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH:19]=[CH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:15][NH:16]2)=[CH:12][CH:11]=1)[C:3]1[CH:4]=[C:5]([NH:9][C:33]([C:31]2[S:32][C:28]([CH3:27])=[CH:29][N:30]=2)=[O:34])[CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 218773495-Methyl-1,3-thiazole-2-carboxylic acidHCID 69370903N-methyl-N-(3-styryl-1H-indazol-6-yl)-benzene-1,3-diamine

Product 1

HCID 698723055-Methyl-thiazole-2-carboxylic acid (3-[methyl-(3-styryl-1H-indazol-6-yl)-amino]-phenyl]-amide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21226138Dichloromethane ethylacetateSolvent2×

Conditions

Temperature
23 °C

Procedure

To a solution of N-methyl-N-(3-styryl-1H-indazol-6-yl)-benzene-1,3-diamine, prepared in Example 11, (26 mg, 0.075 mmol) and 5-methyl-thiazole-2 carboxylic acid (64 mg, 0.45 mmol) in DMF (0.375 mL) at 23° C. under an atmosphere of argon was added HATU (171 mg, 0.45 mmol). After 1 h, TLC analysis (CH2Cl2:EtOAc 8:2) indicated no starting material. The reaction was quenched with saturated NaHCO3(aq) (2 mL) then diluted with EtOAc (15 mL) and the organic phase was washed with brine (3 mL), decanted and concentrated under reduced pressure. The oil was suspended in MeOH (2 mL) and K2CO3 (62 mg, 0.45 mmol) was added. The resulting mixture was stirred at 23° C. under an atmosphere of argon. After 1 h TLC analysis (CH2Cl2:EtOAc 8:2) indicated no starting material. The reaction was diluted with EtOAc (15 mL) and the organic phase was washed with brine (3 mL), decanted and concentrated under reduced pressure to a solid. The crude material was purified by silica gel chromatography (eluting with CH2Cl2:EtOAc 85:15) to give the title compound after purification by semi-prep. HPLC (9.9 mg, 28%). Rf sm 0.25, Rf p 0.39 (hexane:EtOAc 8:2); LCMS (ESI+) [M+H]/z Calc'd 466, found 466. Anal. Calc'd C, (69.65); H, (4.98); N, (15.04); S, (6.89). Found: C, (69.24); H, (5.35); N, (13.97); S, (5.95).

Workup

  1. customThe reaction was quenched with saturated NaHCO3(aq) (2 mL)
  2. additionthen diluted with EtOAc (15 mL)
  3. washthe organic phase was washed with brine (3 mL)
  4. customdecanted
  5. concentrationconcentrated under reduced pressure
  6. washthe organic phase was washed with brine (3 mL)
  7. customdecanted
  8. concentrationconcentrated under reduced pressure to a solid
  9. customThe crude material was purified by silica gel chromatography (eluting with CH2Cl2:EtOAc 85:15)

Sources & evidence

ORD record
ord-0562579cd8bc448ab2d2dce1ff192111
Source dataset
uspto-grants-2005_05
Patent number
US06891044B2

Reaction notes

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