Water → HCID 58710600, compound

HRID 646773Notes

Reaction equation

HRID 646773 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.[OH:25][CH2:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:3]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[O:10])=[N:4][C:5]([C:31]2[CH:30]=[CH:29][CH:28]=[C:27]([CH2:26][OH:25])[CH:32]=2)=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 587105891,1-Dimethylethyl (3S)-3-[[(3-amino-6-bromo-2-pyrazinyl)carbonyl]amino]-1-piperidinecarboxylate

Product 1

HCID 58710600HCID 58710600, compoundYield 93.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

1,1-dimethylethyl (3S)-3-{[(3-amino-6-bromopyrazin-2-yl)carbonyl]amino}piperidine-1-carboxylate (765.0 mg, 1.91 mmol) was dissolved in DMF followed by addition of 3-hydroxymethyl phenylboronic acid (349.0 mg, 2.23 mmol), K2CO3 (660.0 mg, 4.77 mmol) and Pd(PPh3)4 (10 mol %, 220 mg). This mixture was stirred at 90° C. under nitrogen for 12 hours. The reaction mixture was poured into water (150 mL), and extracted with ethyl acetate (3×50 mL). The organic layers were washed with brine (50 mL) then dried over anhydrous sodium sulfate. Filteration, concentration and column chromatography on silica (50% ethylacetate/hexanes) gave a solid which was dried to affored 765.0 mg (92% yield) of 1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-(hydroxymethyl)phenyl]pyrazin-2yl}carbonyl)amino]piperidine-1-carboxylate: MS (EI) for C22H29N5O4: 428.23 (MH+).

Workup

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. washThe organic layers were washed with brine (50 mL)
  3. dry with materialthen dried over anhydrous sodium sulfate
  4. concentrationFilteration, concentration and column chromatography on silica (50% ethylacetate/hexanes)
  5. customgave a solid which

Sources & evidence

ORD record
ord-e8fc5343b1e041c1835a68bacf9faf60
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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