Oxalyl chloride → HCID 67542121, compound

HRID 219933Notes

Reaction equation

HRID 219933 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]1[CH:13]=[C:12]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[C:21]([F:28])[CH:20]=3)[N:15]=2)[CH:11]=[CH:10][C:9]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH3:35].Cl.[CH3:37][O:38][C:39](=[O:42])[CH2:40][NH2:41].CCN(C(C)C)C(C)C>C(Cl)Cl.C1COCC1.CN(C=O)C>[CH3:7][C:8]1[CH:13]=[C:12]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:27]=[CH:26][C:22]([C:23]([NH:41][CH2:40][C:39]([O:38][CH3:37])=[O:42])=[O:24])=[C:21]([F:28])[CH:20]=3)[N:15]=2)[CH:11]=[CH:10][C:9]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH3:35]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 25255868HCID 25255868, compound

Product 1

HCID 67542121HCID 67542121, compoundYield 86.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Oxalyl chloride (63.46 μL; 0.75 mmol) was added to suspension of example 4 (97.10 mg; 0.25 mmol) and DMF (0.50 μL; 0.01 mmol) in DCM (10 mL) and the resulting mixture was stirred at RT for 1 hour. The solution was then evaporated to dryness, the residue taken up in THF (3 mL) and then added to a mixture of glycine methyl ester hydrochloride salt (FLUKA; 50110; 31.39 mg; 0.25 mmol) and DIEA (189.56 μL; 1.10 mmol) in THF (2 mL). The reaction mixture was stirred at RT for 2 hours, filtered through a SPE NH2 column (2 g) and rinsed with ACN. After evaporation of the solvents, the crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5), affording the title compound as a yellow oil (99 mg; 86%). 1H NMR (DMSO-d6, 300 MHz) δ 8.95-8.90 (m, 1H), 8.18 (br s, 1H), 8.10-8.04 (m, 2H), 7.98 (dd, J=10.8, 1.3 Hz, 1H), 7.93-7.88 (m, 1H), 7.40-7.27 (m, 4H), 7.15-7.12 (m, 1H), 4.07 (d, J=5.5 Hz, 2H), 3.69 (s, 3H), 2.14 (s, 3H), 2.04 (s, 3H). LC/MS (Method B): 458.5 (M−H)−, 460.3 (M+H)+. HPLC (Method A) Rt 5.57 min (Purity: 99.2%).

Workup

  1. customThe solution was then evaporated to dryness
  2. stirringThe reaction mixture was stirred at RT for 2 hours
  3. filtrationfiltered through a SPE NH2 column (2 g)
  4. washrinsed with ACN
  5. customAfter evaporation of the solvents
  6. customthe crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5)

Sources & evidence

ORD record
ord-7a1b313b2e4a4ba095102b7c70154419
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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