Thiophosgene → HCID 59464207, compound

HRID 1713735Notes

Reaction equation

HRID 1713735 reaction equation
C(Cl)(Cl)=S.[CH:5]([O:8][C:9]1[CH:10]=[C:11]([CH:13]=[CH:14][CH:15]=1)[NH2:12])([CH3:7])[CH3:6].[C:16](=[O:19])([O-])[O-].[Ca+2].[C:21]([N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:35]=[CH:34][C:33]([NH:36][C:37](=[O:42])[C:38]([NH:40][NH2:41])=O)=[CH:32][CH:31]=2)[CH2:26][CH2:25]1)(=[O:23])[CH3:22].CCN=C=NCCCN(C)C>C(Cl)Cl.O.CN(C=O)C.O>[C:21]([N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:31]=[CH:32][C:33]([NH:36][C:37]([C:38]3[O:19][C:16]([NH:12][C:11]4[CH:13]=[CH:14][CH:15]=[C:9]([O:8][CH:5]([CH3:7])[CH3:6])[CH:10]=4)=[N:41][N:40]=3)=[O:42])=[CH:34][CH:35]=2)[CH2:26][CH2:25]1)(=[O:23])[CH3:22]

Participants

9

Reactant 5

HCID 10040ThiophosgeneHCID 10112Calcium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 5732203-(Propan-2-yloxy)anilineHCID 57830811HCID 57830811, compound2×

Product 1

HCID 59464207HCID 59464207, compoundYield 8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 21908982Water methylene chlorideSolvent

Procedure

Thiophosgene (46 μL, 0.60 mmol) was added dropwise to a stirred solution of 3-isopropoxy aniline (82 mg, 0.543 mmol) and calcium carbonate (272 mg, 2.72 mmol) in DCM/H2O (1:1) (4 mL). This was stirred at room temperature for 1 h. The phases were separated and the organic layer was dried and concentrated in vacuo. The residue was dissolved in DMF (3 mL) and added to a stirred solution of N-[4-(4-acetylpiperazin-1-yl)phenyl]-2-hydrazino-2-oxoacetamide (Intermediate 21, 100 mg, 0.33 mmol) in DMF at 85° C. This mixture was stirred at 85° C. for 1 h then EDAC (105 mg, 0.54 mmol) was added. The mixture was stirred at 100° C. for a further 1 h then allowed to cool and treated with H2O (10 mL). The resulting precipitate was filtered and washed sequentially with DMSO/MeCN/H2O (7:2:1) (5 mL) and ether (5 mL) to give the title compound as a white solid (12 mg, 8%); 1H NMR δ 10.90 (1H, s), 10.82 (s, 1H), 7.67 (2H, d), 7.25 (2H, d), 7.10 (1H, d), 6.97 (2H, d), 6.63 (1H, d), 4.59 (1H, m), 3.58 (4H, br. s), 3.15 (2H, m), 3.09 (2H, m), 2.04 (3H, s), 1.32 (3H, s), 1.30 (3H, s); MS m/e MH+ 465.

Workup

  1. customThe phases were separated
  2. customthe organic layer was dried
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in DMF (3 mL)
  5. stirringThis mixture was stirred at 85° C. for 1 h
  6. stirringThe mixture was stirred at 100° C. for a further 1 h
  7. temperatureto cool
  8. filtrationThe resulting precipitate was filtered
  9. washwashed sequentially with DMSO/MeCN/H2O (7:2:1) (5 mL) and ether (5 mL)

Sources & evidence

ORD record
ord-04221160e4244ceb97cc4e3dc132adc2
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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