tert-Butyl bromoacetate → HCID 66669275, compound

HRID 2176439Notes

Reaction equation

HRID 2176439 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.Br[CH2:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].C(N(CC)C(C)C)(C)C>O1CCCC1.O.CCOC(C)=O>[C:36]([O:35][C:33](=[O:34])[CH2:32][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)([CH3:39])([CH3:38])[CH3:37]

Participants

7

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 81531DiisopropylethylamineHCID 66664953HCID 66664953, compound

Product 1

HCID 66669275HCID 66669275, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of tert-butyl 4-(2-(3-aminophenyl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate (50 mg, 0.117 mmol, 1.0 equiv) in 1.0 mL tetrahydrofuran is added dropwise a solution of tert-butyl bromoacetate (0.069 mL, 0.467 mmol, 4.0 equiv) in 0.5 mL tetrahydrofuran and a solution of N,N-diisopropylethylamine (0.082 mL, 0.467 mmol, 4.0 equiv) in 0.5 mL tetrahydrofuran. The mixture is heated in a microwave reactor for 30 min at 120° C. 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 washed with water and brine, and concentrated in vacuo to give crude tert-butyl 4-(2-(3-(2-tert-butoxy-2-oxoethylamino)phenyl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate as a yellow solid. The residue is then taken on crude to the next reaction, which followed 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)phenylamino)acetic acid (18 mg, 40%) as a tan solid.

Workup

  1. customThe layers are separated
  2. extractionthe aqueous layer is back-extracted with EtOAc
  3. washThe combined organic extracts are washed with water and brine
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7542b7f1f3924e6285f24f4df2a85270
Source dataset
uspto-grants-2015_06
Patent number
US09066948B2

Reaction notes

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