Methyl Acrylate → HCID 57657221, compound

HRID 244820Notes

Reaction equation

HRID 244820 reaction equation
[C:1]([O:5][CH3:6])(=[O:4])[CH:2]=[CH2:3].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:37]1[CH:38]=[CH:39][C:40]2[C:41]3[N:50]([CH2:51][CH2:52][CH2:53][CH2:54][N:55]4[CH2:59][CH2:58][CH2:57][S:56]4(=[O:61])=[O:60])[C:49]([CH2:62][O:63][CH2:64][CH3:65])=[N:48][C:42]=3[C:43]([NH2:47])=[N:44][C:45]=2[CH:46]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[NH2:47][C:43]1[C:42]2[N:48]=[C:49]([CH2:62][O:63][CH2:64][CH3:65])[N:50]([CH2:51][CH2:52][CH2:53][CH2:54][N:55]3[CH2:59][CH2:58][CH2:57][S:56]3(=[O:61])=[O:60])[C:41]=2[C:40]2[CH:39]=[CH:38][C:37](/[CH:3]=[CH:2]/[C:1]([O:5][CH3:6])=[O:4])=[CH:46][C:45]=2[N:44]=1

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 69081980HCID 69081980, compound

Product 1

HCID 57657221HCID 57657221, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
90 °C

Procedure

A 50-mL thick walled glass vessel was charged with palladium (II) acetate (67 mg, 0.3 mmol), acetonitrile (2 mL), methyl acrylate (0.26 g, 3.0 mmol), triethylamine (0.9 g, 9.0 mmol), tri-o-tolylphosphine (0.18 g, 0.6 mmol) and 7-bromo-1-[4-(1,1-dioxidoisothiazolidin-2-yl)butyl]-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (U.S. Patent Application Publication No. US 2004/0147543 Example 152-156, 1.5 g, 3.0 mmol). An additional 13 mL of acetonitrile was added. The reaction mixture was purged with nitrogen then heated to 90° C. The turbid orange mixture was maintained at 90° C. overnight. Anhydrous DMF (30 mL) was added to dissolve the 7-bromoquinoline starting material. The reaction was then heated at 120° C. overnight. The reaction mixture was filtered to remove the catalyst then concentrated to dryness. The desired product was isolated by column chromatography on silica gel (eluting with a gradient of 2%-8% methanol in dichloromethane). The resulting peach solid was taken up in saturated potassium carbonate solution and dichloromethane and stirred overnight at ambient temperature. The organic layer was separated and concentrated to dryness. The residue was recrystallized from acetonitrile to yield 0.65 g of Methyl(2E)-3-[4-amino-1-[4-(1,1-dioxidoisothiazolidin-2-yl)butyl]-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enoate as a pale yellow solid, mp 162-163° C.

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. temperatureThe turbid orange mixture was maintained at 90° C. overnight
  3. additionAnhydrous DMF (30 mL) was added
  4. dissolutionto dissolve the 7-bromoquinoline starting material
  5. temperatureThe reaction was then heated at 120° C. overnight
  6. filtrationThe reaction mixture was filtered
  7. customto remove the catalyst
  8. concentrationthen concentrated to dryness

Sources & evidence

ORD record
ord-fda4063f974e481fa1a5f1b800dd4097
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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