Diisopropylethylamine → HCID 70873918, compound

HRID 2208894Notes

Reaction equation

HRID 2208894 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([N:15]([CH2:28][CH3:29])[C:16]2[C:17]([CH2:26][CH3:27])=[C:18]([CH:22]=[C:23]([Cl:25])[CH:24]=2)[C:19]([OH:21])=O)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:63][CH2:64][C:65]1[C:66](=[O:73])[NH:67][C:68]([CH3:72])=[CH:69][C:70]=1[CH3:71]>CN(C=O)C>[Cl:25][C:23]1[CH:22]=[C:18]([C:19](=[O:21])[NH:63][CH2:64][C:65]2[C:66](=[O:73])[NH:67][C:68]([CH3:72])=[CH:69][C:70]=2[CH3:71])[C:17]([CH2:26][CH3:27])=[C:16]([N:15]([CH2:28][CH3:29])[CH:12]2[CH2:13][CH2:14][CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10][CH2:11]2)[CH:24]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 70873812HCID 70873812, compound

Product 1

HCID 70873918HCID 70873918, compoundYield 54.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 3-[(4-{[(tert-butoxy)carbonyl]amino}cyclohexyl)(ethyl)amino]-5-chloro-2-ethylbenzoic acid (139 mg, 0.33 mmol) in anhydrous DMF (2.0 ml) at 0° C. under nitrogen, was treated with HATU (149 mg, 0.39 mmol) and DIPEA (114 μl, 0.65 mmol). The resulting solution was stirred for 10 minutes and then treated with 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 61 mg, 0.36 mmol). The resulting suspension was stirred at 0° C. for 1 hour and then stirred at room temperature for 98.5 hours. The reaction mixture was treated with HATU (37 mg, 0.1 mmol), stirred for 1 hour and then 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 11 mg, 0.07 mmol). The reaction mixture was stirred at room temperature for a further 23 hours and then partitioned between water (20 ml) and CH2Cl2 (20 ml). The layers were separated and the aqueous phase was extracted with CH2Cl2 (3×10 ml). The combined organics were washed with a saturated solution of NaHCO3 (aq) (40 ml), water (20 ml), brine (2×20 ml), dried (MgSO4), filtered and concentrated in-vacuo. The crude residue was purified by flash column chromatography (10 g SNAP cartridge, Isolera, 0-13% MeOH/CH2Cl2) and triturated from ether/heptane (2.0 ml) with sonication and the liquor decanted. The remaining solid was dried under high vacuum to give the title compound (101 mg, 52%) as a beige solid. LC-MS 93%, 4.54 min (7 minute LC-MS method), m/z=559.2, 561.2. 1H NMR shows a mixture of cis/trans isomers.

Workup

  1. stirringThe resulting suspension was stirred at 0° C. for 1 hour
  2. stirringstirred at room temperature for 98.5 hours
  3. stirringstirred for 1 hour
  4. stirringThe reaction mixture was stirred at room temperature for a further 23 hours
  5. custompartitioned between water (20 ml) and CH2Cl2 (20 ml)
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with CH2Cl2 (3×10 ml)
  8. washThe combined organics were washed with a saturated solution of NaHCO3 (aq) (40 ml), water (20 ml), brine (2×20 ml)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in-vacuo
  12. customThe crude residue was purified by flash column chromatography (10 g SNAP cartridge, Isolera, 0-13% MeOH/CH2Cl2)
  13. customtriturated from ether/heptane (2.0 ml) with sonication
  14. customthe liquor decanted
  15. customThe remaining solid was dried under high vacuum

Sources & evidence

ORD record
ord-a9afaeef24754daca50d73be8368bcf7
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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