1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 90066725, compound

HRID 1487957Notes

Reaction equation

HRID 1487957 reaction equation
[CH:1]1([C:5]2[C:13]([C:14]3[NH:24][C:17]4[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22][C:16]=4[N:15]=3)=[CH:12][C:8]([C:9](O)=[O:10])=[C:7]([CH3:25])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.CCN=C=NCCCN(C)C.Cl.Cl.[NH:39]1[CH2:42][CH:41]([C:43]2[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[CH:45][CH:44]=2)[CH2:40]1>CN(C)C1C=CN=CC=1.CN(C)C=O>[CH:1]1([C:5]2[C:13]([C:14]3[NH:24][C:17]4[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22][C:16]=4[N:15]=3)=[CH:12][C:8]([C:9]([N:39]3[CH2:42][CH:41]([C:43]4[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[CH:45][CH:44]=4)[CH2:40]3)=[O:10])=[C:7]([CH3:25])[CH:6]=2)[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 552549914-(Azetidin-3-yl)benzonitrile hydrochloride2×HCID 90066724HCID 90066724, compound2×

Product 1

HCID 90066725HCID 90066725, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

Into a 100-mL round-bottom flask, was placed a mixture of 4-cyclobutyl-2-methyl-5-(6-methyl-1,4,5,6,7,8-hexahydroimidazo[4,5-d]azepin-2-yl)benzoic acid (compound 82.9, 40 mg, 0.12 mmol), EDC.HCl (45.4 mg, 0.24 mmol, 2.00 equiv), 4-dimethylaminopyridine (29 mg, 0.24 mmol) and 4-(azetidin-3-yl)benzonitrile hydrochloride (compound 5.2, 23 mg, 0.12 mmol) in N,N-dimethylformamide (5 mL). The resulting solution was stirred for 4 h at room temperature then quenched by the addition of water/ice (10 mL). The resulting mixture was extracted with ethyl acetate (2×20 mL) and the combined organic layers were washed with brine (2×10 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure to yield the crude product which was purified by Prep-HPLC using the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, XBridge Shield RP18 OBD Column, 5 um, 19*150 mm; mobile phase, WATER WITH 0.03% NH4OH and CH3CN (30% CH3CN up to 43% in 8 min, up to 100% in 4 min, down to 30% in 2 min); Detector, Waters 2489, 254 & 220 nm. The fractions containing clean product were combined to yield 2.2 mg (4%) of the title compound as a white solid. m/z (ES+) 480 (M+H)+.

Workup

  1. customInto a 100-mL round-bottom flask, was placed
  2. customthen quenched by the addition of water/ice (10 mL)
  3. extractionThe resulting mixture was extracted with ethyl acetate (2×20 mL)
  4. washthe combined organic layers were washed with brine (2×10 mL)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto yield the crude product which
  9. customwas purified by Prep-HPLC
  10. waitmobile phase, WATER WITH 0.03% NH4OH and CH3CN (30% CH3CN up to 43% in 8 min
  11. waitup to 100% in 4 min
  12. waitdown to 30% in 2 min)
  13. additionThe fractions containing clean product

Sources & evidence

ORD record
ord-676db026a6c54e3f81ea8aabf8f1ad59
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

Loading…