Ethyl Acetate → HCID 11510379, compound

HRID 857507Notes

Reaction equation

HRID 857507 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=O.[Br:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[C:20]([C:21]([OH:23])=O)=[CH:19][N:18]3[CH:24]=[CH:25][N:26]=[C:17]3[CH:16]=2)=[C:10]([Cl:27])[CH:9]=1.C1(C[NH:32]O)CC1.CCO[C:37]([CH3:39])=O>C(Cl)Cl.CN(C=O)C>[CH:2]1([CH2:1][O:5][NH:32][C:21]([C:20]2[C:15]([NH:14][C:11]3[CH:12]=[CH:13][C:8]([Br:7])=[CH:9][C:10]=3[Cl:27])=[CH:16][C:17]3[N:18]([CH:24]=[CH:25][N:26]=3)[CH:19]=2)=[O:23])[CH2:39][CH2:37]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 65578Oxalyl chlorideHCID 10034577HCID 10034577, compoundHCID 21866982HCID 21866982, compound

Product 1

HCID 11510379HCID 11510379, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (102 μL of a 2.0 M solution in CH2Cl2) was added to a stirred suspension of 7-(4-bromo-2-chlorophenylamino)imidazo[1,2-a]pyridine-6-carboxylic acid (43) (15 mg, 0.041 mmol) in CH2Cl2 (1 mL) at 0° C. One drop of DMF was added. The reaction mixture was warmed to room temperature, stirred for 25 minutes, and then concentrated. The residue was twice concentrated from toluene and dried in vacuo. The residue was suspended in CH2Cl2 (1 mL), cooled to 0° C. and cyclopropylmethylhydroxylamine (36 mg, 0.409 mmol) was added. The reaction mixture was warmed to room temperature, stirred for 2 hours and diluted with EtOAc. The organic layer was washed with saturated NaHCO3 and brine, dried (Na2SO4) and concentrated. Purification by flash column chromatography using the Biotage system (40:1 CH2Cl2:MeOH to 20:1 CH2Cl2:MeOH) provided the desired product (44a) as a tan solid (6 mg, 31%). MS APCI (−) m/z 433, 435 (M−, Cl, Br pattern) detected: 1H NMR (400 MHz, CDCl3) δ 8.68 (s, 1H), 7.69 (m, 1H), 7.67 (d, 1H), 7.52–7.44 (m, 3H), 7.08 (s, 1H), 3.83 (d, 2H), 0.90 (m, 1H), 0.62 (m, 2H), 0.35 (m, 2H).

Workup

  1. concentrationconcentrated
  2. concentrationThe residue was twice concentrated from toluene
  3. customdried in vacuo
  4. temperaturecooled to 0° C.
  5. temperatureThe reaction mixture was warmed to room temperature
  6. stirringstirred for 2 hours
  7. washThe organic layer was washed with saturated NaHCO3 and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-324d4885c31844eebb540da592bb70b5
Source dataset
uspto-grants-2006_12
Patent number
US07144907B2

Reaction notes

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