Sodium Bicarbonate → HCID 178451889, compound

HRID 18351Notes

Reaction equation

HRID 18351 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[NH:19][C:18]([C@@H:20]4[CH2:24][CH2:23][CH2:22][N:21]4[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[N:17][CH:16]=3)=[CH:11][CH:10]=2)O1.I[C:34]1[CH:39]=[CH:38][C:37]([C:40]2[NH:44][N:43]=[C:42]([C@@H:45]3[CH2:49][CH2:48][CH2:47][N:46]3[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH:41]=2)=[CH:36][CH:35]=1.C([O-])(O)=O.[Na+]>COCCOC.O.C(OCC)(=O)C.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:28]([O:27][C:25]([N:21]1[CH2:22][CH2:23][CH2:24][C@H:20]1[C:18]1[NH:19][C:15]([C:12]2[CH:13]=[CH:14][C:9]([C:34]3[CH:39]=[CH:38][C:37]([C:40]4[NH:44][N:43]=[C:42]([C@@H:45]5[CH2:49][CH2:48][CH2:47][N:46]5[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH:41]=4)=[CH:36][CH:35]=3)=[CH:10][CH:11]=2)=[CH:16][N:17]=1)=[O:26])([CH3:31])([CH3:29])[CH3:30]

Participants

8

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 178451890HCID 178451890, compound

Product 1

HCID 178451889HCID 178451889, compoundYield 43%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (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 (17) (Scheme 9; 0.138 g, 0.314 mmol), (S)-tert-butyl 2-(5-(4-iodophenyl)-1H-pyrazol-3-yl)pyrrolidine-1-carboxylate 8 (0.141 g, 0.321 mmol), NaHCO3 (0.110 g, 1.31 mmol) and Pd(PPh3)4 (0.024 g, 0.0208 mmol) in a mixture of DME (3 mL) and H2O (1 mL) was heated at 80° C. under Ar for 12 hours. The cooled mixture was diluted with ethyl acetate/H2O, the layers separated and the aqueous phase was re-extracted with ethyl acetate (2×). The combined organic layers were washed (H2O, brine) and dried (Na2SO4) and filtered and the solvent was removed in vacuo. The resulting residue was purified by flash chromatography (hexane:ethyl acetate, 2:1 and then ethyl acetate:methanol, 9:1) to give (S)-tert-butyl 2-(5-(4′-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-pyrazol-3-yl)pyrrolidine-1-carboxylate (19) (0.084 g, 43%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 13.01, 12.69, 12.20, 11.91, 11.85 (s, 1H), 7.63-7.85 (m, 8H), 7.50-7.56 (m, 1H), 6.52 (s, 1H), 4.75-4.94 (m, 2H), 3.42-3.58 (m, 2H), 3.30-3.39 (m, 2H, partially obscured by H2O signal), 2.10-2.28 (m, 2H), 1.81-2.01 (m, 6H), 1.40 (s, 7H), 1.20-1.23 (m, 6H), 1.13-1.15 (m, 5H). LCMS: Anal. Calcd. for C36H44N6O4: 624. found: 625 (M+H)+.

Workup

  1. customthe layers separated
  2. extractionthe aqueous phase was re-extracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed (H2O, brine)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe resulting residue was purified by flash chromatography (hexane

Sources & evidence

ORD record
ord-b0860c3b3b514ae890df706f04736235
Source dataset
uspto-grants-2010_06
Patent number
US07741347B2

Reaction notes

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