Aniline → Ethyl 1-[5-[2-(ethylcarbamoylamino)-7-(1-phenyltriazol-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

HRID 712263Notes

Reaction equation

HRID 712263 reaction equation
N[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N(OC(C)(C)C)=O.C[Si]([N:19]=[N+:20]=[N-:21])(C)C.[CH2:22]([NH:24][C:25]([NH:27][C:28]1[S:29][C:30]2[C:36]([C:37]#[CH:38])=[CH:35][C:34]([C:39]3[CH:40]=[N:41][C:42]([N:45]4[CH2:50][CH2:49][C:48]([CH3:56])([C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH2:47][CH2:46]4)=[N:43][CH:44]=3)=[CH:33][C:31]=2[N:32]=1)=[O:26])[CH3:23].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>C(#N)C.O.S([O-])([O-])(=O)=O.[Cu+2]>[CH2:22]([NH:24][C:25]([NH:27][C:28]1[S:29][C:30]2[C:36]([C:37]3[N:19]=[N:20][N:21]([C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH:38]=3)=[CH:35][C:34]([C:39]3[CH:44]=[N:43][C:42]([N:45]4[CH2:46][CH2:47][C:48]([CH3:56])([C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH2:49][CH2:50]4)=[N:41][CH:40]=3)=[CH:33][C:31]=2[N:32]=1)=[O:26])[CH3:23]

Participants

9

Reactant 5

HCID 6115AnilineHCID 10906Tert-Butyl nitriteHCID 78378AzidotrimethylsilaneHCID 23667548Sodium AscorbateHCID 86663977Ethyl 1-[5-[2-(ethylcarbamoylamino)-7-ethynyl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

Product 1

HCID 86663976Ethyl 1-[5-[2-(ethylcarbamoylamino)-7-(1-phenyltriazol-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylateYield 22.6%

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Aniline (18.9 mg, 0.203 mmol) in ACN (2 mL) was cooled to 0° C., t-Butyl nitrite (31.4 mg, 0.305 mmol) was added dropwise, the reaction stirred for 5 minutes, then trimethylsilylazide (50.7 mg, 0.244 mmol) was added in one portion and the mixture allowed to warm to rt and stirred for hours. Ethyl 1-[5-[2-(ethylcarbamoylamino)-7-ethynyl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (100 mg, 0.203 mmol) and sodium ascorbate (8.1 mg, 0.040 mmol) were added, followed by copper sulphate (1.6 mg, 0.010 mmol) in 0.1 mL of water. The reaction was stirred at rt for 18 hours, filtered through a pad of keiselguhr and the solvent removed under vacuum to yield a brown gum. The crude material was purified by preperative HPLC to give the product as an off white solid 28 mg, 22.6% yield.

Workup

  1. stirringstirred for hours
  2. stirringThe reaction was stirred at rt for 18 hours
  3. filtrationfiltered through a pad of keiselguhr
  4. customthe solvent removed under vacuum
  5. customto yield a brown gum
  6. customThe crude material was purified by preperative HPLC

Sources & evidence

ORD record
ord-bbe9190fa1eb4637b13be94f7cf569b8
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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