Triethylamine → HCID 86704615, compound

HRID 1508567Notes

Reaction equation

HRID 1508567 reaction equation
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([CH2:34][CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[C:24]([CH3:40])[N:23]=[C:22](SC)[N:21]=3)[C@H:14]2[CH3:43])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.[F:57][C:58]1([F:62])[CH2:61][NH:60][CH2:59]1.CCN(CC)CC>C(Cl)Cl.C1COCC1>[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([CH2:34][CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[C:24]([CH3:40])[N:23]=[C:22]([N:60]4[CH2:61][C:58]([F:62])([F:57])[CH2:59]4)[N:21]=3)[C@H:14]2[CH3:43])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 70297m-Chloroperbenzoic acidHCID 27582483,3-DifluoroazetidineHCID 86704616HCID 86704616, compound

Product 1

HCID 86704615HCID 86704615, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of the title compound from Step A (20 mg, 0.030 mmol) and mCPBA (10.50 mg, 0.061 mmol) in CH2Cl2 (2 mL) was stirred at room temperature for 1 h. TLC showed no SM. The mixture was diluted with CH2Cl2 (10 mL) and washed with Na2S2O3 and Na2HCO3, and dried over Na2SO4. The solvent was removed. A mixture of the residue, 3,3-difluoro-azetidine (19.70 mg, 0.152 mmol) and Et3N (3.08 mg, 0.030 mmol) in THF was heated at 140° C. under microwave for 4 h. The solvent was removed and the title compound was purified by preparative TLC plate as a white solid using EtOAc/hexane as the elute (2/8). LCMS=703.4 (M+H)+. The final compound was a mixture of two separable atropisomers, which could be separated by chiral OD column using EtOH/heptane as the elute.

Workup

  1. washwashed with Na2S2O3 and Na2HCO3
  2. dry with materialdried over Na2SO4
  3. customThe solvent was removed
  4. temperaturewas heated at 140° C. under microwave for 4 h
  5. customThe solvent was removed
  6. customthe title compound was purified by preparative TLC plate as a white solid
  7. washelute (2/8)
  8. additiona mixture of two separable atropisomers, which
  9. customcould be separated by chiral OD column

Sources & evidence

ORD record
ord-93cfe5d5ec204228b5d23b3f5a970f1f
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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