Carbonic Acid → HCID 117778962, compound

HRID 2206645Notes

Reaction equation

HRID 2206645 reaction equation
Br[C:2]1[C:3]([NH:9][CH:10]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[CH3:11])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[C:25]([O:30][CH2:31][CH3:32])(=[O:29])[C:26]#[C:27][CH3:28].[Cl-].[Li+].C(=O)(O)O>CN(C)C=O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[C:21]([O:20][C:18]([N:15]1[CH2:16][CH2:17][CH:12]([CH:10]([N:9]2[C:3]3[N:4]=[C:5]([Cl:8])[N:6]=[CH:7][C:2]=3[C:26]([C:25]([O:30][CH2:31][CH3:32])=[O:29])=[C:27]2[CH3:28])[CH3:11])[CH2:13][CH2:14]1)=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

7

Reactant 4

HCID 767Carbonic AcidHCID 78043Ethyl 2-butynoateHCID 433294Lithium ChlorideHCID 117779043HCID 117779043, compound

Product 1

HCID 117778962HCID 117778962, compoundYield 17.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

Into the vial were added tert-butyl 4-(1-((5-bromo-2-chloropyrimidin-4-yl)amino)ethyl)piperidine-1-carboxylate (400 mg, 0.95 mmol) and ethyl but-2-ynoate (128 mg, 1.14 mmol), palladium(II) diacetate (42 mg, 0.19 mmol), lithium chloride (51.8 mg, 1.23 mmol), carbonic acid (393 mg, 2.85 mmol) in N,N-dimethyl formamide. The mixture was degassed for 10 min and refilled with nitrogen, and irradiated in the microwave on a Biotage smith synthesizer at 120° C. for 40 min. The reaction mixture was cooled down and added to water (30 ml), and extracted with ethyl acetate (10 ml×3). The organic layer was dried over sodium sulfate and concentrated. The crude product was purified by column chromatography on silica gel (petroleum/ethyl acetate: 20:1 to 10:1) to give compound ethyl 7-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)ethyl)-2-chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (75 mg, yield: 17.4%) as a yellow oil. LRMS (M+H+) m/z: calcd 450.2. found 451.

Workup

  1. customThe mixture was degassed for 10 min
  2. additionrefilled with nitrogen
  3. customirradiated in the microwave on a Biotage smith synthesizer at 120° C. for 40 min
  4. temperatureThe reaction mixture was cooled down
  5. additionadded to water (30 ml)
  6. extractionextracted with ethyl acetate (10 ml×3)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography on silica gel (petroleum/ethyl acetate: 20:1 to 10:1)

Sources & evidence

ORD record
ord-c86c99148ad14b47ae3e772382b74edd
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

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