Hydrochloric Acid → HCID 66620267, compound

HRID 2392464Notes

Reaction equation

HRID 2392464 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%). {2-Methyl-1-[2-(5-(5-[4-(2-{1-[2-(methylperoxymethyl-amino)-2-phenyl-acetyl]-pyrrolidin-2-yl]-3H-imidazol-4-yl)-phenyl]-3a,6a-dihydro-thieno[3,2-b]thiophen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester: [2-Oxo-1-phenyl-2-(2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidin-1-yl)-ethyl]-carbamic acid methyl ester (204 mg, 0.385 mmol), (1-{2-[5-(5-Bromo-3a,6a-dihydro-thieno[3,2-b]thiophen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (137 mg, 0.268 mmol), Pd(PPh3)4 (31 mg, 0.0268 mmol) and K2CO3 (2M in H2O, 0.4 mL, 0.8 mmol) were combined in 1,2-dimethoxyethane (2.7 mL). After 10 min of degassing with bubbling N2, the reaction mixture was heated to 85° C. for 19 h. After this period, it was cooled and diluted MeOH. The suspension was filtered over a thiol SPE cartridge to remove the palladium, then concentrated. The crude residue was purified by HPLC to afford the title compound (103 mg, 46%). MS (ESI) m/z 835 [M+H]+.

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-bcd824fda32e43d1978443ba350eaced
Source dataset
uspto-grants-2012_09
Patent number
US08273341B2

Reaction notes

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