Sodium Bicarbonate → HCID 68098173, compound

HRID 1510828Notes

Reaction equation

HRID 1510828 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]2[C:6]([NH2:9])=[N:7][O:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[NH:30][C:29]([C@@H:31]4[CH2:35][CH2:34][CH2:33][N:32]4[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[N:28][CH:27]=3)=[CH:22][CH:21]=2)O1.C([O-])(O)=O.[Na+].O.CCOC(C)=O>COCCOC.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>[NH2:9][C:6]1[C:5]2[CH:10]=[CH:11][C:2]([C:20]3[CH:21]=[CH:22][C:23]([C:26]4[NH:30][C:29]([C@@H:31]5[CH2:35][CH2:34][CH2:33][N:32]5[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[N:28][CH:27]=4)=[CH:24][CH:25]=3)=[CH:3][C:4]=2[O:8][N:7]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 106086216-bromobenzo[d]isoxazol-3-amineHCID 22728543Water ethylacetateHCID 56605289(s)-tert-Butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1h-imidazol-2-yl)pyrrolidine-1-carboxylate

Product 1

HCID 68098173HCID 68098173, compoundYield 26.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 6-bromobenzo[d]isoxazol-3-amine (1.78 g, 8.36 mmol), (S)-tert-butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (3.95 g, 8.99 mmol), Pd(Ph3P)4 (0.42 g, 0.364 mmol) and NaHCO3 (1.93 g, 23.0 mmol) was suspended in DME (60 mL) and H2O (20 mL) and the solution was degassed by evacuating and back-filling with N2 (repeated 5 times). The mixture was then heated at 70° C. overnight. LCMS indicated the reaction to be incomplete. A further portion of Pd(Ph3P)4 (0.10 g, 0.087 mmol) was added and heating continued for a further 12 h. The cooled reaction mixture was poured into H2O/EtOAc and the layers separated. The aq layer was extracted with EtOAc (×2) and the combined org layers were washed (H2O, brine), then dried (Na2SO4) and concentrated. The residue was purified by BIOTAGE® (TLC 5:4.5:0.5 hexane:EtOAc:MeOH) solvent A was 1:1 hex:EtOAc and solvent B was 20% MeOH in EtOAc to afford a red-orange foam (1.0 g). This material was purified by prep HPLC (CH3CN—H2O—NH4OAc) giving a light yellow foam (404.4 mg, 11%). 1H NMR (400 MHz, DMSO-d6) δ 11.85-12.21 (m, 1H), 7.85 (app t, J=8.0, 8.6, 2H), 7.72-7.73 (m, 4H), 7.54-7.60 (m, 2H), 6.41 (s, 2H), 4.76-4.83 (m, 1H), 3.54 (s, br, 1H), 3.31-3.37 (m, 1H, partially obscured by H2O), 2.14-2.25 (m, 1H), 1.79-2.04 (m, 3H), 1.40, 1.15 (s, 9H, rotamers). LCMS: Anal, Calcd. for C25H27N5O3: 445; found: 446 (M+H)+.

Workup

  1. customH2O (20 mL) and the solution was degassed
  2. customby evacuating and back-filling with N2 (repeated 5 times)
  3. customthe reaction
  4. temperatureheating
  5. customThe cooled reaction mixture
  6. customthe layers separated
  7. extractionThe aq layer was extracted with EtOAc (×2)
  8. washthe combined org layers were washed (H2O, brine)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customThe residue was purified by BIOTAGE® (TLC 5:4.5:0.5 hexane:EtOAc:MeOH) solvent A

Sources & evidence

ORD record
ord-a3db5829dbd146dabc5d87100d93212b
Source dataset
uspto-grants-2012_07
Patent number
US08211928B2

Reaction notes

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