Dimethylamine → HCID 89612847, compound

HRID 1402427Notes

Reaction equation

HRID 1402427 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:42]=[C:43]([CH:52]=[CH:53][CH:54]=2)[O:44][C@H:45]([CH3:51])[CH2:46][NH:47][C:48](N)=[O:49])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:55]S(O)(=O)=[O:57].CNC>C1COCC1>[CH:48]([OH:49])=[O:57].[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:54]=[CH:53][CH:52]=[C:43]([O:44][C@H:45]([CH3:51])[CH2:46][N:47]([CH3:48])[CH3:55])[CH:42]=2)[N:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 674DimethylamineHCID 131732152HCID 131732152, compound

Product 1

HCID 89612847HCID 89612847, compoundYield 34.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of Intermediate 151e (89 mg, 0.12 mmol) in THF (0.8 mL) was treated with a 2M solution of dimethylamine in THF (1.2 mL, 2.3 mmol) and the mixture was stirred at 60° C. for 42 h. The cooled solution was concentrated in vacuo, and the residue was partitioned between DCM and water. The phases were separated and the aqueous layer was extracted with DCM (×2). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo to a brown glass. The glass was purified by HPLC (Phenomenex Gemini C18 column, 5-95% MeCN in H2O, 0.1% HCO2H) over 25 mins. Concentration of the fractions in vacuo gave a pale yellow glass. The glass was triturated with ether to give a solid that was filtered off to give the title compound as a fawn coloured solid (16 mg, 19%). LCMS (Method 5): Rt 3.68 min, m/z 720.5 [MH+]. 1H NMR (400 MHz, do-DMSO): 0.91 (3H, d, J=6.5 Hz), 1.24 (3H, d, J=6.1 Hz), 1.27 (9H, s), 1.46-1.56 (2H, m), 1.61-1.72 (2H, m), 1.74-1.98 (4H, m), 1.99-2.16 (2H, m), 2.17 (6H, s), 2.32-2.39 (1H, m), 2.86-2.95 (1H, m), 3.13-3.19 (1H, m), 3.29-3.34 (1H, m), 4.56-4.65 (1H, m), 4.79-4.86 (1H, m), 5.52 (1H, t, J=4.4 Hz), 6.32 (1H, s), 6.94-6.99 (1H, m), 7.03-7.12 (3H, m), 7.19 (1H, dd, J=9.9, 2.0 Hz), 7.24-7.41 (5H, m), 7.64 (1H, d, J=10.2 Hz), 7.68-7.70 (1H, m), 8.15 (1H, s), 8.20 (1H, s).

Workup

  1. concentrationThe cooled solution was concentrated in vacuo
  2. customthe residue was partitioned between DCM and water
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with DCM (×2)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo to a brown glass
  8. customThe glass was purified by HPLC (Phenomenex Gemini C18 column, 5-95% MeCN in H2O, 0.1% HCO2H) over 25 mins
  9. customConcentration of the fractions in vacuo gave a pale yellow glass
  10. customThe glass was triturated with ether
  11. customto give a solid
  12. filtrationthat was filtered off

Sources & evidence

ORD record
ord-9b4a4e73362e4a1c8f0c9d31929528de
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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