Hydrochloric Acid → HCID 178502171, compound

HRID 417656Notes

Reaction equation

HRID 417656 reaction equation
[CH3:1][O:2][C:3](=[O:44])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][C:30]([C:33](=[O:43])[CH2:34][NH:35][C:36](OC(C)(C)C)=[O:37])=[CH:29][CH:28]=3)=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].Cl.CCN(C(C)C)C(C)C.[C:55]([O:59][C:60]([N:62]1[CH2:70][C:69]2[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=2)[CH:63]1C(O)=O)=[O:61])([CH3:58])([CH3:57])[CH3:56].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O1CCOCC1.CN(C=O)C.CCOC(C)=O>[C:55]([O:59][C:60]([N:62]1[CH2:70][C:69]2[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=2)[CH:63]1[C:36](=[O:37])[NH:35][CH2:34][C:33]([C:30]1[CH:31]=[CH:32][C:27]([C:24]2[CH:23]=[CH:22][C:21]([C:19]3[N:20]=[C:16]([CH:12]4[CH2:13][CH2:14][CH2:15][N:11]4[C:9](=[O:10])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:44])[CH:6]([CH3:8])[CH3:7])[NH:17][CH:18]=3)=[CH:26][CH:25]=2)=[CH:28][CH:29]=1)=[O:43])=[O:61])([CH3:57])([CH3:58])[CH3:56]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2×HCID 27559672-((tert-butoxy)carbonyl)-2,3-dihydro-1H-isoindole-1-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178502175HCID 178502175, compound

Product 1

HCID 178502171HCID 178502171, compoundYield 111.5%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

[1-(2-{-4-[4′-(2-tert-Butoxycarbonylamino-acetyl)-biphenyl-4-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (107.0 mg, 0.177 mmol) was dissolved in DCM (1 mL) and HCl in dioxane (4M, 1 mL) was added and stirring at room temperature was continued. After 45 minutes, all volatiles were removed in vacuo. The crude material was used in the next step without further purification. The crude material was dissolved in DMF (0.6 mL) and DIEA (68.4 mg, 0.531 mmol) was added. A solution of racemic 1,3-dihydro-isoindole-1,2-dicarboxylic acid 2-tert-butyl ester (46.6 mg, 0.177 mmol), HATU (67.3 mg, 0.177 mmol) and DIEA (22.8 mg, 0.177 mmol) in DMF (0.4 mL) was added. The reaction was stirred at room temperature. After 15 minutes, the reaction was diluted with EtOAc and was washed with brine, saturated sodium bicarbonate solution, brine, and was dried over sodium sulfate. Filtration and removal of solvents in vacuo gave the crude material (147.8 mg), which was used in the next step without further purification.

Workup

  1. customall volatiles were removed in vacuo
  2. customThe crude material was used in the next step without further purification
  3. dissolutionThe crude material was dissolved in DMF (0.6 mL)
  4. stirringThe reaction was stirred at room temperature
  5. waitAfter 15 minutes
  6. washwas washed with brine, saturated sodium bicarbonate solution, brine
  7. dry with materialwas dried over sodium sulfate
  8. filtrationFiltration and removal of solvents in vacuo

Sources & evidence

ORD record
ord-6ae2bc6e97f34e24bcf70b68a38471b6
Source dataset
uspto-grants-2012_01
Patent number
US08088368B2

Reaction notes

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