Diisopropylamine → HCID 66668558, compound

HRID 2176440Notes

Reaction equation

HRID 2176440 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[C:16]3[S:23][C:22]([C:24]4[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=4)[C:27](O)=[O:28])=[N:21][N:17]3[C:18](=[O:20])[CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:33]([O:37][C:38](=[O:41])[CH2:39][NH2:40])([CH3:36])([CH3:35])[CH3:34].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(NC(C)C)(C)C>CN(C)C=O.O.CCOC(C)=O>[C:33]([O:37][C:38](=[O:41])[CH2:39][NH:40][C:27]([C:26]1[CH:25]=[C:24]([C:22]2[S:23][C:16]3=[N:15][C:14]([N:11]4[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]4)=[CH:19][C:18](=[O:20])[N:17]3[N:21]=2)[CH:32]=[CH:31][CH:30]=1)=[O:28])([CH3:36])([CH3:35])[CH3:34]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 151417Glycine tert-butyl esterHCID 2724699PyBOPHCID 66668080HCID 66668080, compound

Product 1

HCID 66668558HCID 66668558, compoundYield 73.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(7-(4-(tert-butoxycarbonyl)piperazin-1-yl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)benzoic acid (45 mg, 0.098 mmol, 1.0 equiv), is prepared using the procedure similarly described in Example 7, is dissolved in 1 mL in dimethylformamide. To the solution is added glycine tert-butyl ester (0.016 ml, 0.118 mmol, 1.2 equiv), PyBOP (77 mg, 0.148 mmol, 1.5 equiv), then N,N-diisopropylamine (0.052 ml, 0.295 mmol, 3.0 equiv). The mixture stirred at room temperature for 18 h. Upon completion, the mixture is taken up in water and EtOAc. The layers are separated and the aqueous layer is back-extracted with EtOAc. The combined organic extracts are then washed with water twice, then brine, dried (MgSO4) and concentrated in vacuo to give a yellow oil which is purified by chromatography (silica gel, 2-5% MeOH/dichloromethane) to give tert-butyl 4-(2-(3-(2-tert-butoxy-2-oxoethylcarbamoyl)phenyl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate (41 mg, 73.0% yield) as a yellow oil. The residue is then taken on to the next reaction, which follows the same deprotection procedure as above to give 2-(3-(5-oxo-7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)benzamido)acetic acid (16 mg, 53.7% yield) as a white solid.

Workup

  1. customThe layers are separated
  2. extractionthe aqueous layer is back-extracted with EtOAc
  3. washThe combined organic extracts are then washed with water twice
  4. dry with materialbrine, dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto give a yellow oil which
  7. customis purified by chromatography (silica gel, 2-5% MeOH/dichloromethane)

Sources & evidence

ORD record
ord-77e71280b1dd4df2a85e7f61bcca8e18
Source dataset
uspto-grants-2015_06
Patent number
US09066948B2

Reaction notes

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