Potassium Carbonate → 2-amino-N-[4-(5-oxo-7-piperazin-1-yl-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)-2-pyridinyl]acetamide

HRID 624677Notes

Reaction equation

HRID 624677 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[S:30][C:11]3=[N:12][C:13]([N:17]4[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]4)=[CH:14][C:15](=[O:16])[N:10]3[N:9]=2)[CH:5]=[CH:4][N:3]=1.CC(OC([NH:38][CH2:39][C:40]([NH2:42])=[O:41])=O)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:38][CH2:39][C:40]([NH:42][C:2]1[CH:7]=[C:6]([C:8]2[S:30][C:11]3=[N:12][C:13]([N:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)=[CH:14][C:15](=[O:16])[N:10]3[N:9]=2)[CH:5]=[CH:4][N:3]=1)=[O:41]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 109100641,1-Dimethylethyl N-(2-amino-2-oxoethyl)carbamateHCID 89705380tert-butyl 4-(2-(2-chloropyridin-4-yl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate

Product 1

HCID 716211702-amino-N-[4-(5-oxo-7-piperazin-1-yl-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)-2-pyridinyl]acetamideYield 135.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-(2-(2-chloropyridin-4-yl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate (160 mg, 0.36 mmol) in THF (5 ml) are added Boc-gly-NH2 (124 mg, 0.72 mmol), XantPhos (124 mg, 0.14 mmol), Pd(OAc)2 (24 mg, 0.07 mmol) and K2CO3 (197 mg, 1.44 mmol). The microwave tube is purged with nitrogen for 1 min then sealed. The mixture is microwaved at 90° C. for 2 h. After cooling to room temperature, EtOAc (30 ml) and water (30 ml) are added. The organic layer is separated, washed with brine and dried over sodium sulfate. After the removal of organic solvent in vacuo, the residue is purified through Biotage column chromatography (MeOH/DCM=1/100 to 5/20) to give the desired product (188 mg, 90%).

Workup

  1. customThe microwave tube is purged with nitrogen for 1 min
  2. customthen sealed
  3. customThe mixture is microwaved at 90° C. for 2 h
  4. additionEtOAc (30 ml) and water (30 ml) are added
  5. customThe organic layer is separated
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. customAfter the removal of organic solvent in vacuo
  9. customthe residue is purified through Biotage column chromatography (MeOH/DCM=1/100 to 5/20)

Sources & evidence

ORD record
ord-b02518598c9d49dfb219dadbdbf1b820
Source dataset
uspto-grants-2016_04
Patent number
US09303044B2

Reaction notes

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