1,2-Dichloroethane → HCID 66668008, compound

HRID 2176438Notes

Reaction equation

HRID 2176438 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[S:30][C:11]3=[N:12][C:13]([N:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]4)=[CH:14][C:15](=[O:16])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:31]([NH:38][CH2:39][C:40](O)=[O:41])([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].C(Cl)CCl>CN(C=O)C.O.C(OCC)(=O)C>[C:34]([O:33][C:31]([NH:38][CH2:39][C:40]([NH:1][C:2]1[CH:3]=[C:4]([C:8]2[S:30][C:11]3=[N:12][C:13]([N:17]4[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:21][CH2:22]4)=[CH:14][C:15](=[O:16])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1)=[O:41])=[O:32])([CH3:37])([CH3:36])[CH3:35]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 78288N-(tert-butoxycarbonyl)glycineHCID 66664953HCID 66664953, compound

Product 1

HCID 66668008HCID 66668008, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Crude tert-butyl 4-(2-(3-aminophenyl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate (60 mg, 0.140 mmol) is taken up in DMF (1.5 mL) and to it is added the Boc-glycine (37 mg, 0.210 mmol) then EDC (40.3 mg, 0.210 mmol). The mixture is stirred at room temperature for 24 hours and the reaction mixture is then taken up in water and ethyl acetate. The layers are separated and the aqueous layer is extracted with ethyl acetate. The combined organic extracts are then washed with water twice, then brine, dried over MgSO4, and concentrated in vacuo to give a yellow solid which is purified via column chromatography with 2-7% MeOH/DCM gradient to give tert-butyl 4-(2-(3-(2-(tert-butoxycarbonylamino)acetamido)phenyl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate (crude material confirmed by LCMS analysis). The residue is then taken up in 2 mL of dichloromethane and trifluoroacetic acid (1 ml, 13.0 mmol) is added and the mixture is stirred for 18 hours. The solution is then concentrated in vacuo and washed with dichloroethane to give a crude yellow solid that is dissolved in methanol and purified by preparative HPLC to give 2-amino-N-(3-(5-oxo-7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)phenyl)acetamide (40 mg, 49%) as a tan solid after HPLC purification.

Workup

  1. customThe layers are separated
  2. extractionthe aqueous layer is extracted with ethyl acetate
  3. washThe combined organic extracts are then washed with water twice
  4. dry with materialbrine, dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto give a yellow solid which
  7. customis purified via column chromatography with 2-7% MeOH/DCM gradient

Sources & evidence

ORD record
ord-1fbb579e58444688804e6c43c3d59d8e
Source dataset
uspto-grants-2015_06
Patent number
US09066948B2

Reaction notes

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