Hydrochloric Acid → HCID 178502141, compound

HRID 1185867Notes

Reaction equation

HRID 1185867 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][S:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:33]=[CH:32][C:31]4[C:26](=[CH:27][CH:28]=[C:29]([C:34]5[N:35]=[C:36]([CH:39]6[CH2:45][C:42]7([CH2:44][CH2:43]7)[CH2:41][N:40]6[C:46](=[O:56])[CH:47]([NH:51][C:52]([O:54][CH3:55])=[O:53])[CH:48]([CH3:50])[CH3:49])[NH:37][CH:38]=5)[CH:30]=4)[CH:25]=3)=[CH:20][CH:19]=2)=[CH:16][N:17]=1)=O)(C)(C)C.Cl.CCN(C(C)C)C(C)C.[CH3:67][O:68][C:69]([NH:71][CH:72]([CH:76]1[CH2:81][CH2:80][O:79][CH2:78][CH2:77]1)[C:73]([OH:75])=O)=[O:70].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>[CH3:55][O:54][C:52](=[O:53])[NH:51][CH:47]([C:46]([N:40]1[CH:39]([C:36]2[NH:37][CH:38]=[C:34]([C:29]3[CH:28]=[CH:27][C:26]4[C:31](=[CH:32][CH:33]=[C:24]([C:21]5[CH:22]=[CH:23][C:18]([C:15]6[NH:14][C:13]([CH:9]7[N:8]([C:73](=[O:75])[CH:72]([NH:71][C:69]([O:68][CH3:67])=[O:70])[CH:76]8[CH2:81][CH2:80][O:79][CH2:78][CH2:77]8)[CH2:12][CH2:11][S:10]7)=[N:17][CH:16]=6)=[CH:19][CH:20]=5)[CH:25]=4)[CH:30]=3)[N:35]=2)[CH2:45][C:42]2([CH2:44][CH2:43]2)[CH2:41]1)=[O:56])[CH:48]([CH3:50])[CH3:49]

Participants

9

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 585162412-(methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acidHCID 178502142HCID 178502142, compound

Product 1

HCID 178502141HCID 178502141, compoundYield 11.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

2-{5-[4-(6-{2-[5-(2-Methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-1H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-thiazolidine-3-carboxylic acid tert-butyl ester (49.9 mg, 0.064 mmol) was dissolved in DCM (0.33 mL) and HCl in dioxane (4M, 0.33 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 (0.5 mL) and DIEA (24.6 mg, 0.191 mmol) was added. A solution of 2-(L) methoxycarbonylamino-(tetrahydro-pyran-4-yl)-acetic acid (13.8 mg, 0.064 mmol), HATU (24.1 mg, 0.064 mmol) and DIEA (8.2 mg, 0.064 mmol) in DMF (0.5 mL) was added. The reaction was stirred at room temperature. After 18 hrs all volatiles were removed in vacuo. The crude material, which was purified by RP-HPLC (eluent: water/MeCN w/0.1% TFA) to yield the product (6.2 mg) as a TFA salt.

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 (0.5 mL)
  4. stirringThe reaction was stirred at room temperature
  5. customAfter 18 hrs all volatiles were removed in vacuo
  6. customThe crude material, which was purified by RP-HPLC (eluent: water/MeCN w/0.1% TFA)

Sources & evidence

ORD record
ord-66f431c57ce04efc9a77a601fdba3f91
Source dataset
uspto-grants-2014_03
Patent number
US08669234B2

Reaction notes

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