Dimethylamine → 5-{5-[(Dimethylamino)methyl]-3-thienyl}-3-[(1,1-dioxidotetrahydro-3-thienyl)methyl]-1H-indole-7-carboxamide

HRID 656162

反応式

HRID 656162 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:14][CH:15]1[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16]1.[CH:22]([C:24]1[S:28][CH:27]=[C:26](B(O)O)[CH:25]=1)=O.C(=O)([O-])[O-].[K+].[K+].[CH3:38][NH:39][CH3:40].C1COCC1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>O1CCOCC1.O.CC(O)=O.CS(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:38][N:39]([CH2:22][C:24]1[S:28][CH:27]=[C:26]([C:2]2[CH:3]=[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=2)[NH:7][CH:6]=[C:5]3[CH2:14][CH:15]2[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16]2)[CH:25]=1)[CH3:40]

参加物

12

反応物 6

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 110841152-Formylthiophene-4-boronic acidHCID 593326215-Bromo-3-[(1,1-dioxidotetrahydro-3-thienyl)methyl]-1H-indole-7-carboxamide

生成物 1

HCID 593327775-{5-[(Dimethylamino)methyl]-3-thienyl}-3-[(1,1-dioxidotetrahydro-3-thienyl)methyl]-1H-indole-7-carboxamide収率 82.3%

試薬・触媒・溶媒 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 176Acetic Acid溶媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

5-bromo-3-[(1,1-dioxidotetrahydro-3-thienyl)methyl]-1H-indole-7-carboxamide (120 mg, 0.323 mmol), (5-formyl-3-thienyl)boronic acid (76 mg, 0.485 mmol, 1.5 eq), PdCl2(dppf) (23.65 mg, 0.032 mmol, 0.1 eq), potassium carbonate (134 mg, 0.970 mmol, 3 eq) were diluted in a mixture of 1,4-dioxane (3 mL) and water (1 mL), in a 2-5 mL biotage microwave reaction tube. The mixture was degassed by bubbling nitrogen through for 5 minutes and was then heated in a microwave at high absorption for 15 minutes at 120° C. The reaction was filtered through a thiol SPE cartridge (polymer labs) and was concentrated. Then a solution of 2 M dimethylamine in THF (553 mg, 1.242 mmol, 10 eq), HOAc (1 mL), NaBH(OAc)3 (263 mg, 1.242 mmol, 10 eq) were added in DMSO) (2 mL, and the reaction mixture was stirred at room temperature overnight. Then the solvent was evaporated, EtOAc and water were added, the layers were separated, and the aqueous layer extracted with EtOAc. The combined layers were washed with satured NaCl, dried, concentrated and purified by Gilson HPLC with trifluoroacetic acid buffer. The desired product fractions were combined and concentrated in an EZ2 Genevac evaporator, giving 35.3 mg (82.3%) of the title compound.

後処理

  1. customThe mixture was degassed
  2. customby bubbling nitrogen through for 5 minutes
  3. filtrationThe reaction was filtered through a thiol SPE cartridge (polymer labs)
  4. concentrationwas concentrated
  5. customThen the solvent was evaporated
  6. additionEtOAc and water were added
  7. customthe layers were separated
  8. extractionthe aqueous layer extracted with EtOAc
  9. washThe combined layers were washed with satured NaCl
  10. customdried
  11. concentrationconcentrated
  12. custompurified by Gilson HPLC with trifluoroacetic acid buffer
  13. concentrationconcentrated in an EZ2 Genevac evaporator

出典と根拠

ORDレコード
ord-11c50123244f42afad5511886c70adad
出典データセット
uspto-grants-2011_12
特許番号
US08071584B2

関連ノート

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