Dimethylformamide → HCID 11682941, compound

HRID 408525Notes

Reaction equation

HRID 408525 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([OH:15])=O)[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.CN(C)C=O.[CH3:21][O:22][C:23]1[CH:35]=[CH:34][CH:33]=[CH:32][C:24]=1[CH2:25][C:26]1[S:30][C:29]([NH2:31])=[N:28][CH:27]=1.C(N(CC)CC)C>S(Cl)(Cl)=O.O1CCOCC1>[CH3:21][O:22][C:23]1[CH:35]=[CH:34][CH:33]=[CH:32][C:24]=1[CH2:25][C:26]1[S:30][C:29]([NH:31][C:13]([C:10]2([C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)[CH2:11][CH2:12]2)=[O:15])=[N:28][CH:27]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 143496081-(1,3-Dioxaindan-5-yl)cyclopropane-1-carboxylic acidHCID 53418238HCID 53418238, compound

Product 1

HCID 11682941HCID 11682941, compoundYield 54.2%

Reagents, catalysts & solvents 2

HCID 24386Thionyl ChlorideSolventHCID 312751,4-DioxaneSolvent

Procedure

1-Benzo[1,3]dioxol-5-yl-cyclopropanecarboxylic acid (1.87 g, 9.08 mmol) was dissolved in thionyl chloride (5 mL) under nitrogen for 30 minutes. A catalytic amount of N,N-dimethylformamide was added and stirring continued for an additional 30 minutes. The excess thionyl chloride was evaporated and the resulting residue was dissolved in 1,4 dioxane (15 mL). This solution was slowly added under nitrogen to 5-(2-methoxy-benzyl)-thiazol-2-ylamine (2.00 g, 9.08 mmol) dissolved in 1,4 dioxane (20 mL) containing triethylamine (3.5 mL, 25 mmol). The solution was allowed to stir for 2 hours. The reaction mixture was filtered, the precipitate was washed three times with 1,4 dioxane (20 mL), and the combined filtrate was evaporated to dryness and purified by column chromatography on silica gel using a gradient of 0-30% ethyl acetate in hexanes. The pure fractions were combined and evaporated to dryness to yield an off-white solid. The product was recrystallized twice from ethyl acetate/hexanes to yield the pure product (2.01 g, 4.92 mmol, 54.2%). ESI-MS m/z calc. 408.11. found 409.3 (M+1)+. Retention time of 3.48 minutes. 1H NMR (400 MHz, DMSO-d6) δ 1.11 (m, 2H), 1.43 (m, 2H), 3.80 (s, 3H), 3.97 (s, 2H), 6.01 (s, 2H), 6.87 (m, 3H), 6.98 (m, 2H), 7.16 (m, 2H), 7.22 (m, 1H), 10.76 (s, 1H).

Workup

  1. customThe excess thionyl chloride was evaporated
  2. dissolutionthe resulting residue was dissolved in 1,4 dioxane (15 mL)
  3. stirringto stir for 2 hours
  4. filtrationThe reaction mixture was filtered
  5. washthe precipitate was washed three times with 1,4 dioxane (20 mL)
  6. customthe combined filtrate was evaporated to dryness
  7. custompurified by column chromatography on silica gel using a gradient of 0-30% ethyl acetate in hexanes
  8. customevaporated to dryness
  9. customto yield an off-white solid
  10. customThe product was recrystallized twice from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-347f841c09da46f39da19097e6a5416a
Source dataset
uspto-grants-2014_06
Patent number
US08759335B2

Reaction notes

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