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

HRID 1862118ノート

反応式

HRID 1862118 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒HCID 21226138Dichloromethane ethylacetate溶媒2 回

反応条件

温度
23 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-aae019a220b045efa0d9be07a8c25f4a
出典データセット
uspto-grants-2003_03
特許番号
US06534524B1

反応ノート

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