Sodium Bicarbonate → HCID 67220801, compound

HRID 1510832Notes

Reaction equation

HRID 1510832 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7](Br)=[CH:8][CH:9]=2)[N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[N:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:32]=[CH:31][C:30]([C:33]3[NH:37][C:36]([C@@H:38]4[CH2:42][CH2:41][CH2:40][N:39]4[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[N:35][CH:34]=3)=[CH:29][CH:28]=2)O1.C([O-])(O)=O.[Na+]>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:10]2[C:5](=[CH:6][C:7]([C:27]3[CH:28]=[CH:29][C:30]([C:33]4[NH:37][C:36]([C@@H:38]5[CH2:42][CH2:41][CH2:40][N:39]5[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[N:35][CH:34]=4)=[CH:31][CH:32]=3)=[CH:8][CH:9]=2)[N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[N:3]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 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-carboxylateHCID 58287776HCID 58287776, compound

Product 1

HCID 67220801HCID 67220801, compoundYield 40.3%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 3-amino-6-bromo-1H-indazole-1-carboxylate (1.17 g, 3.73 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 (1.62 g, 3.68 mmol), NaHCO3 (0.96 g, 11 mmol) and Pd(PPh3)4 (212 mg, 0.184 mmol) was degassed and then heated at 80° C. After heating for 24 h the reaction mixture was poured into EtOAc/H2O (500/100 mL) and the mixture was shaken and the layers separated. The aq phase was extracted once more with EtOAc and the combined organic layers were washed (H2O, brine), dried (Na2SO4), and concentrated in vacuo. The residue was purified by BIOTAGE® (40+M, TLC 2:1 EtOAc:hex) affording a light yellow foam (807.8 mg) which was repurified by BIOTAGE® (TLC 6:3.5:0.5 hex:EtOAc:MeOH) to give the title compound as a light yellow solid (413.9 mg, 36%). 1H NMR (400 MHz, DMSO-d6) δ 11.86-12.22 (m, 1H), 8.20 (s, 1H), 7.85-7.92 (m, 3H), 7.75-7.76 (m, 1H), 7.68 (d, J=8.1 Hz, 1H), 7.53-7.62 (m, 2H), 6.35 (s, 2H), 4.75-4.86 (m, 1H), 3.49-3.58 (m, 1H), 3.35-3.39 (m, 1H), 2.10-2.26 (m, 1H), 1.80-2.01 (m, 3H), 1.60 (s, 9H), 1.40 and 1.15 (s, 9H, rotamers). LCMS: Anal. Calcd. for C30H36N6O4: 544; found: 545 (M+H)+.

Workup

  1. customwas degassed
  2. temperatureAfter heating for 24 h the reaction mixture
  3. additionwas poured into EtOAc/H2O (500/100 mL)
  4. customthe layers separated
  5. extractionThe aq phase was extracted once more with EtOAc
  6. washthe combined organic layers were washed (H2O, brine)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by BIOTAGE® (40+M, TLC 2:1 EtOAc:hex)

Sources & evidence

ORD record
ord-57f6618d137842ee80c8898148e3507f
Source dataset
uspto-grants-2012_07
Patent number
US08211928B2

Reaction notes

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