Hydrochloric Acid → HCID 178502143, compound

HRID 79900Notes

Reaction equation

HRID 79900 reaction equation
[CH3:1][O:2][C:3](=[O:50])[NH:4][CH:5]([C:9]([N:11]1[CH:17]([C:18]2[NH:19][CH:20]=[C:21]([C:23]3[CH:32]=[CH:31][C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:33]5[CH:38]=[CH:37][C:36]([C:39](=[O:49])[CH2:40][NH:41]C(OC(C)(C)C)=O)=[CH:35][CH:34]=5)[CH:29]=4)[CH:24]=3)[N:22]=2)[CH2:16][C:13]2([CH2:15][CH2:14]2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].Cl.CCN(C(C)C)C(C)C.[C:61]([N:68]1[CH2:72][CH2:71][S:70][C@H:69]1[C:73]([OH:75])=O)([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62].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:64]([O:63][C:61]([N:68]1[CH2:72][CH2:71][S:70][CH:69]1[C:73](=[O:75])[NH:41][CH2:40][C:39]([C:36]1[CH:37]=[CH:38][C:33]([C:28]2[CH:27]=[CH:26][C:25]3[C:30](=[CH:31][CH:32]=[C:23]([C:21]4[N:22]=[C:18]([CH:17]5[CH2:16][C:13]6([CH2:15][CH2:14]6)[CH2:12][N:11]5[C:9](=[O:10])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:50])[CH:6]([CH3:7])[CH3:8])[NH:19][CH:20]=4)[CH:24]=3)[CH:29]=2)=[CH:34][CH:35]=1)=[O:49])=[O:62])([CH3:65])([CH3:66])[CH3:67]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14775612(S)-3-Boc-thiazolidine-2-carboxylic acidHCID 178502144HCID 178502144, compound

Product 1

HCID 178502143HCID 178502143, compoundYield 102.4%

Reagents, catalysts & solvents 4

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

Procedure

{1-[6-(4-{6-[4-(2-tert-Butoxycarbonylamino-acetyl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-5-aza-spiro[2.4]heptane-5-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (395.0 mg, 0.581 mmol) was dissolved in DCM (4 mL) and HCl in dioxane (4M, 4 mL) was added and stirring at room temperature was continued. After 60 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 (2.0 mL) and DIEA (110.8 mg, 0.860 mmol) was added. A solution of N-Boc (S) thiazolidine-2-carboxylic acid (100.0 mg, 0.430 mmol), HATU (163.0 mg, 0.430 mmol) and DIEA (55.4 mg, 0.430 mmol) in DMF (1 mL) was added. The reaction was stirred at room temperature. After 20 minutes, the reaction was diluted with EtOAc and was washed with brine, sodium hydroxyl solution (1 M), brine, and was dried over sodium sulfate. Filtration and removal of solvents in vacuo gave the crude material (350 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 (2.0 mL)
  4. stirringThe reaction was stirred at room temperature
  5. waitAfter 20 minutes
  6. washwas washed with brine, sodium hydroxyl solution (1 M), brine
  7. dry with materialwas dried over sodium sulfate
  8. filtrationFiltration and removal of solvents in vacuo

Sources & evidence

ORD record
ord-3c2e7139f0894e868c81ec3046691657
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Reaction notes

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