Cyclohexaneacetic acid → HCID 10097120, compound

HRID 1294743Notes

Reaction equation

HRID 1294743 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([N:30]([CH2:33][CH3:34])[CH2:31][CH3:32])=[O:29])=[CH:24][CH:23]=2)[N:9]2[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)[CH:5]=[CH:6][CH:7]=1.[CH:35]1([CH2:41][C:42](O)=[O:43])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:35]1([CH2:41][C:42]([NH:1][C:2]2[CH:3]=[C:4]([C@@H:8]([N:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)[C:22]3[CH:27]=[CH:26][C:25]([C:28]([N:30]([CH2:31][CH3:32])[CH2:33][CH3:34])=[O:29])=[CH:24][CH:23]=3)[CH:5]=[CH:6][CH:7]=2)=[O:43])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1

Participants

6

Reactant 4

HCID 21363Cyclohexaneacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11590834HCID 11590834, compound

Product 1

HCID 10097120HCID 10097120, compoundYield 91,332%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a room temperature solution of INTERMEDIATE 5a (250 mg; 0.54 mmol) in DMF (5 mL) was added cyclohexyl acetic acid (92 mg; 0.65 mmol), DIPEA (0.38 mL; 2.16 mmol) and HATU (0.31 g; 0.81 mmol). The reaction mixture was stirred for 22 hours then was concentrated under reduced pressure. The residue was dissolved in dichloromethane, washed with sodium hydroxide (2N) then with HCl (1M). The organic phase was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue was dissolved in dichloromethane (10 mL) and TFA (1.5 mL) was added. The reaction mixture was stirred for 4 hours then was washed with saturated sodium bicarbonate. The organic phase was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. Column chromatography eluting with 5% methanol in dichloromethane gave COMPOUND 77 (242 g; 92% for two steps). Purity (HPLC-215 nm): >99%; Optical purity (Chiral HPLC-215 nm): >99%. 1H NMR (400 MHz, CD3OD) δ 0.87-0.93 (m, 2H), 0.98 (t, J=7.13 Hz, 3H), 1.08-1.14 (m, 3H), 1.20-1.23 (m, 2H), 1.52-1.71 (br s, 6H), 1.72-1.77 (m, 1H), 2.12 (d, J=7.03 Hz, 2H), 3.09-3.14 (m, 2H), 3.18-3.23 (m, 6H), 3.26-3.33 (br s, 3H), 3.48-3.52 (m, 1H), 5.08 (s, 1H), 7.20 (d, J=4.49 Hz, 2H), 7.24-7.31 (m, 3H), 7.57 (d, J=7.81 Hz, 2H), 7.83 (s, 1H). Found: C, 58.11; H, 8.99; N, 7.46. C30H42N4O2×0.4HCl×6.5H2O has C, 57.90; H, 8.97; N, 9.00%. [α]D17=+4.6 deg [c 0.46, MeOH].

Workup

  1. concentrationthen was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in dichloromethane
  3. washwashed with sodium hydroxide (2N)
  4. dry with materialThe organic phase was dried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  8. additionTFA (1.5 mL) was added
  9. stirringThe reaction mixture was stirred for 4 hours
  10. washthen was washed with saturated sodium bicarbonate
  11. dry with materialThe organic phase was dried over anhydrous sodium sulphate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. washColumn chromatography eluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-1cb77753d2f846dd90cfb3b33f619b1a
Source dataset
uspto-grants-2007_07
Patent number
US07241764B2

Reaction notes

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