4-Toluenesulfonyl chloride → HCID 178481314, compound

HRID 1624152Notes

Reaction equation

HRID 1624152 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.[Cl:21][C:22]1[CH:23]=[C:24]([N:28]=[C:29]=O)[CH:25]=[CH:26][CH:27]=1.S(Cl)(C1C=CC(C)=CC=1)(=O)=O.CC[N:44](CC)CC>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:21][C:22]1[CH:23]=[C:24]([NH:28][C:29]2[O:15][C:14]([C@@:12]3([CH3:18])[NH:13][C:8](=[NH:44])[N:9]([CH3:20])[C:10](=[O:19])[CH2:11]3)=[N:16][N:17]=2)[CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 17968Benzene, 1-chloro-3-isocyanato-HCID 67303828(S)-2-(tert-butoxycarbonyl)-1,4-dimethyl-6-oxo-hexahydropyrimidine-4-carbohydrazide

Product 1

HCID 178481314HCID 178481314, compoundYield 17.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of (S)-2-(tert-butoxycarbonyl)-1,4-dimethyl-6-oxo-hexahydropyrimidine-4-carbohydrazide (CY1, R6=Me, 0.030 g, 0.10 mmol) in DCM (0.25 mL) was added 3-chlorophenylisocyanate (0.015 mL, 0.20 mmol, 2 eq). The mixture was stirred at RT for 3 h and volatiles were then removed in vacuo. The residue was treated with TsCl (0.020 g, 0.10 mmol, 1 eq), Et3N (0.083 mL, 0.60 mmol, 6 eq), and DMAP (0.002 g, 0.016 mmol, 0.16 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 (10%) of (S)-6-(5-(3-chlorophenylamino)-1,3,4-oxadiazol-2-yl)-2-imino-3,6-dimethyl-tetrahydropyrimidin-4(1H)-one (DA1; R6=Me). 1HNMR (CD3OD, 300 MHz): 7.78 (t, 1H), 7.47 (m, 2H), 7.17 (dt, 1H), 3.53 (m, 2H), 3.36 (s, 3H), 1.78 (s, 3H). MS (ESI): MH+=335.3, HPLC (A) Rt=5.710 min.

Workup

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

Sources & evidence

ORD record
ord-b7410f39315c4fb198108b03dbc62c99
Source dataset
uspto-grants-2014_07
Patent number
US08778980B2

Reaction notes

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