Tetrahydrofuran → 2-Nitro-5-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,3-triazol-4-yl)phenyl]thiophene-3-carboxamide

HRID 385748Notes

Reaction equation

HRID 385748 reaction equation
OC(C1N=CC([C:11]2[S:15][C:14]([N+:16]([O-:18])=[O:17])=[C:13]([C:19]([NH2:21])=[O:20])[CH:12]=2)=CC=1)(C)C.CC1(C)C(C)(C)OB([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[N:37]=[N:38][N:39]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[CH:40]=3)=[CH:32][CH:31]=2)O1.C1COCC1.C([O-])([O-])=O.[Na+].[Na+]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N+:16]([C:14]1[S:15][C:11]([C:30]2[CH:31]=[CH:32][C:33]([C:36]3[N:37]=[N:38][N:39]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:46])([CH3:47])[CH3:48])[CH:40]=3)=[CH:34][CH:35]=2)=[CH:12][C:13]=1[C:19]([NH2:21])=[O:20])([O-:18])=[O:17]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 595258015-[6-(1-Hydroxy-1-methylethyl)pyridin-3-yl]-2-nitrothiophene-3-carboxamide2×HCID 595263874-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,3-triazole

Product 1

HCID 595258022-Nitro-5-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,3-triazol-4-yl)phenyl]thiophene-3-carboxamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

5-Bromo-2-nitrothiophene-3-carboxamide (Intermediate 10 Step 4) (470 mg, 1.87 mmol), 4-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,3-triazole (751 mg, 1.87 mmol), and Pd(PPh3)4 (108 mg, 0.094 mmol) were combined in a vial and evacuated/backfilled with nitrogen. THF (4.4 mL) and 2 N Na2CO3 (1.9 mL) were added. The reaction mixture was heated to 90° C. overnight. The black reaction was diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered, combined with silica, and evaporated. Flash chromatography (dry load, 50-100% EtOAc/hexanes) afforded a brown solid that was triturated with CH2Cl2 and filtered to isolate the title compound as a yellow solid. The mother liquor was concentrated, triturated again, and filtered to isolate an additional batch of the title compound.

Workup

  1. customThe black reaction
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. dry with materialFlash chromatography (dry load, 50-100% EtOAc/hexanes)
  8. customafforded a brown solid that
  9. customwas triturated with CH2Cl2
  10. filtrationfiltered

Sources & evidence

ORD record
ord-5038b56270954a998ca39a71e982b0ed
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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