Methylboronic Acid → HCID 118187817, compound

HRID 928696Notes

Reaction equation

HRID 928696 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[C:21](Cl)=[N:20][CH:19]=[C:18]([C:23]2[N:24]=[C:25]([N:32]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[C:33]3[CH:38]=[CH:37][C:36]([N:39]4[CH2:44][CH2:43][N:42]([CH:45]5[CH2:48][O:47][CH2:46]5)[CH2:41][CH2:40]4)=[C:35]([O:49][CH2:50][CH2:51][O:52][CH:53]4[CH2:58][CH2:57][CH2:56][CH2:55][O:54]4)[CH:34]=3)[C:26]3[N:27]([CH:29]=[CH:30][N:31]=3)[CH:28]=2)[N:17]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:66]B(O)O>C(=O)([O-])[O-].[Na+].[Na+].COCCOC.C(Cl)Cl.O.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>[C:1]([O:5][C:6]([N:8]([C:16]1[C:21]([CH3:66])=[N:20][CH:19]=[C:18]([C:23]2[N:24]=[C:25]([N:32]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[C:33]3[CH:38]=[CH:37][C:36]([N:39]4[CH2:44][CH2:43][N:42]([CH:45]5[CH2:48][O:47][CH2:46]5)[CH2:41][CH2:40]4)=[C:35]([O:49][CH2:50][CH2:51][O:52][CH:53]4[CH2:58][CH2:57][CH2:56][CH2:55][O:54]4)[CH:34]=3)[C:26]3[N:27]([CH:29]=[CH:30][N:31]=3)[CH:28]=2)[N:17]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 2

HCID 139377Methylboronic AcidHCID 118187814HCID 118187814, compound

Product 1

HCID 118187817HCID 118187817, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
150 °C

Procedure

A microwave vial was charged with tert-butyl tert-butoxycarbonyl(6-(8-((tert-butoxycarbonyl)(4-(4-(oxetan-3-yl)piperazin-1-yl)-3-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)phenyl)amino)imidazo[1,2-a]pyrazin-6-yl)-3-chloropyrazin-2-yl)carbamate XXXIV (258 mg, 0.28 mmol), methylboronic acid (503 mg, 8.4 mmol), Pd(PPh3)4 (32 mg, 0.03 mmol) in sodium carbonate (0.8 mL, 1M in H2O) and DME (2.5 mL). The mixture was heated at 150° C. for 20 min. The reaction was cooled to room temperature, diluted with DCM and H2O. The aqueous layer was separated and extracted with DCM. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography ISCO Rf (4 g column) eluting with a gradient of 100% DCM—100% 75/18/7 DCM/Et2O/MeOH to provide the desired compound tert-butyl tert-butoxycarbonyl(6-(8-((tert-butoxycarbonyl)(4-(4-(oxetan-3-yl)piperazin-1-yl)-3-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)phenyl)amino)imidazo[1,2-a]pyrazin-6-yl)-3-methylpyrazin-2-yl)carbamate XXXV.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe aqueous layer was separated
  3. extractionextracted with DCM
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by column chromatography ISCO Rf (4 g column)
  9. washeluting with a gradient of 100% DCM—100% 75/18/7 DCM/Et2O/MeOH

Sources & evidence

ORD record
ord-5dd1e90d68fa449ca22d555288760e2b
Source dataset
uspto-grants-2016_03
Patent number
US09290505B2

Reaction notes

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