Chloroacetyl chloride → HCID 54756017, compound

HRID 530966Notes

Reaction equation

HRID 530966 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([CH:18]([CH3:20])[CH3:19])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[Cl:30][CH2:31][C:32](Cl)=[O:33]>C1COCC1>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:18]([CH3:20])[CH3:19])[N:9]=[C:8]([C:4]3[CH:3]=[C:2]([NH:1][C:32](=[O:33])[CH2:31][Cl:30])[CH:7]=[CH:6][CH:5]=3)[C:16]=12

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 70113938HCID 70113938, compound

Product 1

HCID 54756017HCID 54756017, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of THF (20 mL), compound 22 (200 mg, 0.75 mmol) and DIPEA (143 μL, 0.821 mmol) was cooled to 0° C. Chloroacetylchloride (54 μL, 0.67 mmol) was added and the reaction was allowed to proceed for 1 hour and afterwards concentrated in vacuo. The residue was dissolved in dichloromethane (20 mL) and washed with saturated sodium bicarbonate (20 mL). The aqueous layer was extracted with dichloromethane (2×20 mL). The combined organic layers were dried with MgSO4, filtered and concentrated in vacuo. The product was purified by preparative RP-HPLC and lyophilized (30.4 mg, 13% yield): 1H NMR (400 MHz, DMSO) δ 10.57 (s, 1H), 8.41 (s, 1H), 7.95 (s, 1H), 7.67 (d, J=7.6, 1H), 7.53 (t, J=7.9, 1H), 7.41 (d, J=7.7, 1H), 5.11 (hept, J=6.7, 1H), 4.30 (s, 2H), 1.51 (d, J=6.7, 6H); 13C NMR (100 MHz, DMSO) δ 165.06, 154.82, 151.89, 150.90, 144.68, 139.03, 132.62, 128.28, 123.81, 120.02, 119.24, 96.92, 48.84, 43.55, 21.77; [M+H]+ calculated for C16H17ClN6O 345.1, found 345.4.

Workup

  1. concentrationafterwards concentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (20 mL)
  3. washwashed with saturated sodium bicarbonate (20 mL)
  4. extractionThe aqueous layer was extracted with dichloromethane (2×20 mL)
  5. dry with materialThe combined organic layers were dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe product was purified by preparative RP-HPLC

Sources & evidence

ORD record
ord-dc1a629dc371413aac9357a5d3c81a3b
Source dataset
uspto-grants-2016_05
Patent number
US09353116B2

Reaction notes

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