Ammonia → HCID 178508034, compound

HRID 707249Notes

Reaction equation

HRID 707249 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([NH:15][C:16]2[C:21](I)=[CH:20][N:19]=[CH:18][N:17]=2)[CH2:12]1.C([O-])(=O)C.[Cs+].[NH3:28]>CS(C)=O.[Cu]>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([NH:15][C:16]2[C:21]([NH2:28])=[CH:20][N:19]=[CH:18][N:17]=2)[CH2:12]1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 5152919Cesium acetateHCID 178506556HCID 178506556, compound2×

Product 1

HCID 178508034HCID 178508034, compoundYield 34.5%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

Trans-N1-(benzo[d]thiazol-2-yl)-N3-(5-iodopyrimidin-4-yl)cyclobutane-1,3-diamine (synthesized analogous to intermediate 33 using 5-iodo-4-chloropyrimidine in place of 3-bromo-2-chloropyridine, 0.130 g, 0.307 mmol), copper (0.010 g, 0.157 mmol), and cesium acetate (0.250 g, 1.302 mmol) were suspended in dry dimethylsulfoxide (2 mL) in a microwave vessel. Ammonia (2.0 M solution in methanol, 1.0 ml, 2.000 mmol) was added and the mixture sealed under argon. It was heated at 80° C. in an oil bath for 4½ hours then cooled to 60° C. and stirred for another 14 hours. The reaction mixture was partitioned between ethyl acetate (200 mL), water (200 mL), and ammonium hydroxide (30 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (0-10% (2 N ammonia in methanol) in dichloromethane gradient) gave the desired N4-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)pyrimidine-4,5-diamine (0.033 g, 0.106 mmol, 34.4% yield).

Workup

  1. customthe mixture sealed under argon
  2. temperaturethen cooled to 60° C.
  3. customThe reaction mixture was partitioned between ethyl acetate (200 mL), water (200 mL), and ammonium hydroxide (30 mL)
  4. dry with materialThe organic was dried with magnesium sulfate
  5. customevaporated to dryness under reduced pressure
  6. customPurification

Sources & evidence

ORD record
ord-8e2749c3531d41b8921d9f818d8c0c1e
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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