Hydrochloric Acid → HCID 66620267, compound

HRID 71998Notes

Reaction equation

HRID 71998 reaction equation
C(O[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([B:24]3[O:28][C:27]([CH3:30])([CH3:29])[C:26]([CH3:32])([CH3:31])[O:25]3)=[CH:20][CH:19]=2)=[CH:16][N:17]=1)=[O:7])(C)(C)C.Cl.[CH3:34][O:35][C:36]([NH:38][CH:39]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)C(O)=O)=[O:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl.CCOC(C)=O>[CH3:34][O:35][C:36](=[O:37])[NH:38][CH:39]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:6](=[O:7])[N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([B:24]3[O:25][C:26]([CH3:32])([CH3:31])[C:27]([CH3:30])([CH3:29])[O:28]3)=[CH:20][CH:19]=2)=[CH:16][N:17]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 596264N-Methoxycarbonyl-2-phenylglycineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574497592-{4-[4-(4,4,5,5-Tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]-1h-imidazol-2-yl}pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66620267HCID 66620267, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-{5-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (530 mg, 1.21 mmol) was dissolved in DCM (4 mL) and treated with HCl (4M in dioxane, 1 mL, 4 mmol). The reaction mixture was stirred at RT for 19 h then the solid was filtered off and rinsed with DCM. After being thoroughly dried (461 mg, 92%), a portion of this solid (200 mg, 0.485 mmol) was combined with Methoxycarbonylamino-phenyl-acetic acid (122 mg, 0.582 mmol) and HATU (221 mg, 0.582 mmol) were suspended in DCM (5 mL) and K3PO4 (309 mg, 1.455 mmol) was added. After stirring 24 h, the reaction mixture was diluted with EtOAc and washed with 1M LiOH and brine. The organic layer was dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (75% to 100% EtOAc) to provide the title compound (204 mg, 79%).

Workup

  1. filtrationthe solid was filtered off
  2. washrinsed with DCM
  3. customAfter being thoroughly dried (461 mg, 92%)
  4. stirringAfter stirring 24 h
  5. washwashed with 1M LiOH and brine
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica column chromatography (75% to 100% EtOAc)

Sources & evidence

ORD record
ord-16c540cced714a579f323c405938b1dc
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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