Cesium carbonate → Tert-butyl 4-(5-cyano-1,3-benzothiazol-2-yl)-3-oxopiperazine-1-carboxylate

HRID 1465746Notes

Reaction equation

HRID 1465746 reaction equation
Cl[C:2]1[S:3][C:4]2[CH:10]=[CH:9][C:8]([C:11]#[N:12])=[CH:7][C:5]=2[N:6]=1.NC1C=C(C=CC=1Cl)C#N.[O:23]=[C:24]1[NH:29][CH2:28][CH2:27][N:26]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:25]1.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-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:11]([C:8]1[CH:9]=[CH:10][C:4]2[S:3][C:2]([N:29]3[CH2:28][CH2:27][N:26]([C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])[CH2:25][C:24]3=[O:23])=[N:6][C:5]=2[CH:7]=1)#[N:12]

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 1044643-Amino-4-chlorobenzonitrileHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 219856792-Chlorobenzo[d]thiazole-5-carbonitrile

Product 1

HCID 121332446Tert-butyl 4-(5-cyano-1,3-benzothiazol-2-yl)-3-oxopiperazine-1-carboxylateYield 35%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a flask charged with 2-chloro-1,3-benzothiazole-5-carbonitrile [prepared from 3-amino-4-chlorobenzonitrile following the procedure described in US Publication 2009/0197862, Example 267] (146 mg, 0.75 mmol) and a stir bar was added tert-butyl 3-oxopiperazine-1-carboxylate (225 mg, 1.1 mmol), Pd2(dba)3 (69 mg, 0.075 mmol), Xantphos (87 mg, 0.15 mmol), cesium carbonate (370 mg, 1.1 mmol), and dioxane (10 mL). The mixture was purged three times with nitrogen, and heated to 100° C. under N2 for 16 hours. The reaction was diluted with EtOAc, adsorbed onto silica gel, and purified by silica gel chromatography (Hexanes:EtOAc 1:1) to provide tert-butyl 4-(5-cyano-1,3-benzothiazol-2-yl)-3-oxopiperazine-1-carboxylate (95 mg, 35% yield). The carboxylate was further treated with TFA to remove the Boc group. After removal of TFA, the residue was dissolved in aqueous sodium carbonate, extracted with DCM, dried over sodium sulfate, and concentrated to provide the free base of 2-(2-oxopiperazin-1-yl)-1,3-benzothiazole-5-carbonitrile. LC-MS (IE, m/z): 259 [M+1]+.

Workup

  1. customThe mixture was purged three times with nitrogen
  2. additionThe reaction was diluted with EtOAc
  3. custompurified by silica gel chromatography (Hexanes:EtOAc 1:1)

Sources & evidence

ORD record
ord-4cb51944f5fe42b2a59126c5a73fb7df
Source dataset
uspto-grants-2015_04
Patent number
US08999991B2

Reaction notes

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