4-Toluenesulfonyl chloride → HCID 178481313, compound

HRID 884472Notes

Reaction equation

HRID 884472 reaction equation
C(OC([C@H:8]1[NH:13][C:12]([CH3:18])([C:14]([NH:16][NH2:17])=[O:15])[CH2:11][C:10](=[O:19])[N:9]1[CH3:20])=O)(C)(C)C.CC[N:23](CC)CC.[C:28]([C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33](Cl)=O)#[N:29].S(Cl)(C1C=CC(C)=CC=1)(=O)=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[NH:23]=[C:8]1[NH:13][C@@:12]([C:14]2[O:15][C:33]([C:32]3[CH:31]=[C:30]([CH:38]=[CH:37][CH:36]=3)[C:28]#[N:29])=[N:17][N:16]=2)([CH3:18])[CH2:11][C:10](=[O:19])[N:9]1[CH3:20]

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471Triethylamine2×HCID 3084833-Cyanobenzoyl chlorideHCID 67303828(S)-2-(tert-butoxycarbonyl)-1,4-dimethyl-6-oxo-hexahydropyrimidine-4-carbohydrazide

Product 1

HCID 178481313HCID 178481313, compoundYield 16.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent4×

Procedure

To a solution of (S)-2-(tert-butoxycarbonyl)-1,4-dimethyl-6-oxo-hexahydropyrimidine-4-carbohydrazide (CY1; R6=Me, 0.037 g, 0.12 mmol) in DCM (0.3 mL) at 0° C. was added Et3N (0.035 mL, 0.24 mmol, 2 eq) followed by 3-cyanobenzoyl chloride (0.027 g, 0.16 mmol, 1.3 eq). The mixture was stirred at RT for 6 h. The mixture was diluted with DCM (20 mL), washed with H2O (10 mL) and saturated brine (10 mL), and concentrated in vacuo. The residue was then treated with TsCl (0.035 g, 0.18 mmol, 1.5 eq), Et3N (0.046 mL, 0.31 mmol, 2.6 eq), and DMAP (0.002 g, 0.016 mmol, 0.13 eq) in DCM (0.25 mL) at RT for 16 h. The mixture was diluted with DCM (20 mL), washed with H2O (10 mL) and saturated brine (10 mL), and concentrated in vacuo. The residue was treated with 30% TFA/DCM (1 mL) at RT for 1 h. The mixture was concentrated in vacuo and the residue was purified on reverse phase HPLC (B) to give 0.006 g (12%) of 3-(5-((S)-2-imino-1,4-dimethyl-6-oxo-hexahydropyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)benzonitrile as a white solid (CZ1; R6=Me). 1H NMR (CD3OD, 300 MHz): 8.49 (m, 2H), 8.12 (d, 1H), 7.92 (t, 1H), 3.75 (m, 2H), 3.36 (s, 3H), 1.82 (s, 3H). MS (ESI): MH+=311.2, HPLC (A) Rt=4.175 min.

Workup

  1. washwashed with H2O (10 mL) and saturated brine (10 mL)
  2. concentrationconcentrated in vacuo
  3. washwashed with H2O (10 mL) and saturated brine (10 mL)
  4. concentrationconcentrated in vacuo
  5. additionThe residue was treated with 30% TFA/DCM (1 mL) at RT for 1 h
  6. concentrationThe mixture was concentrated in vacuo
  7. customthe residue was purified on reverse phase HPLC (B)

Sources & evidence

ORD record
ord-60394cb1de754fa3b89178a2347498dc
Source dataset
uspto-grants-2012_08
Patent number
US08242112B2

Reaction notes

Loading…