Water → HCID 86678998, compound

HRID 2203363Notes

Reaction equation

HRID 2203363 reaction equation
[NH2:1][C:2]1[C:3]2[C:29]([CH3:36])([C:30]3[O:31][C:32](=[O:35])[NH:33][N:34]=3)[C:28](=[O:37])[NH:27][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=3)[N:10]([CH2:18][CH2:19][C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])[N:9]=2)[N:7]=1.C(=O)([O-])[O-].[K+].[K+].I[CH:45]([CH3:47])[CH3:46].O>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:3]2[C:29]([CH3:36])([C:30]3[O:31][C:32](=[O:35])[N:33]([CH:45]([CH3:47])[CH3:46])[N:34]=3)[C:28](=[O:37])[NH:27][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=3)[N:10]([CH2:18][CH2:19][C:20]([F:25])([F:26])[C:21]([F:22])([F:23])[F:24])[N:9]=2)[N:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 86678999HCID 86678999, compound

Product 1

HCID 86678998HCID 86678998, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the intermediate from Step A above (120 mg, 0.22 mmol) and finely powdered potassium carbonate (36.9 mg, 0.264 mmol) in DMF (3 mL), was added 2-iodopropane (35.9 mg, 0.21 mmol) and the reaction was stirred for 7 hours at room temperature. Water (4 mL) and ethyl acetate (15 mL) were then added to the reaction mixture. The water layer was extracted with ethyl acetate (3×). The combined organic layer was dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by reverse phase HPLC to give the indicated compound as a white solid. Chiral separation using SFC on a Chiralcel OJ column provided both enantiomers of the title compound. 1H NMR (500 MHz, CDCl3) δ 1.31 (d, J=6.4 Hz, 3H); 1.33 (d, J=6.4 Hz, 3H); 1.77 (s, 3H); 2.84 (t, J=7.8 Hz, 2H); 4.36 (t, J=6.6 Hz, 1H); 4.78 (t, J=7.6 Hz, 2H); 5.34 (s, 2H); 7.27 (d, J=8.7 Hz, 1H); 7.49 (s, 1H); 8.51 (d, J=8.7 Hz, 1H). m/z=587.13 (M+H).

Workup

  1. extractionThe water layer was extracted with ethyl acetate (3×)
  2. dry with materialThe combined organic layer was dried over Na2SO4
  3. customevaporated under reduced pressure
  4. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-7534d8a757d54347a1628a5cad45c83f
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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