Triethylamine → HCID 86730359, compound

HRID 1427059Notes

Reaction equation

HRID 1427059 reaction equation
S(Cl)(Cl)=O.N1C2C=CC=CC=2N=N1.[C:14]([O:18][C:19]([N:21]1[CH2:24][CH:23]([C:25]2[CH:33]=[CH:32][C:28]([C:29]([OH:31])=O)=[CH:27][CH:26]=2)[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(N(CC)CC)C.[NH2:41][C:42]1[CH:47]=[C:46]([O:48][C:49]2[CH:50]=[C:51]3[C:55](=[CH:56][C:57]=2[O:58][CH2:59][CH2:60][CH2:61][O:62][CH3:63])[N:54]([C:64]([NH:66][CH3:67])=[O:65])[CH:53]=[CH:52]3)[CH:45]=[CH:44][N:43]=1>ClCCl.CN(C)C1C=CN=CC=1.O1CCCC1.C(OCC)(=O)C.O>[CH3:63][O:62][CH2:61][CH2:60][CH2:59][O:58][C:57]1[CH:56]=[C:55]2[C:51]([CH:52]=[CH:53][N:54]2[C:64](=[O:65])[NH:66][CH3:67])=[CH:50][C:49]=1[O:48][C:46]1[CH:45]=[CH:44][N:43]=[C:42]([NH:41][C:29]([C:28]2[CH:27]=[CH:26][C:25]([CH:23]3[CH2:22][N:21]([C:19]([O:18][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:20])[CH2:24]3)=[CH:33][CH:32]=2)=[O:31])[CH:47]=1

Participants

11

Reactant 5

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 86730347HCID 86730347, compoundHCID 86730360HCID 86730360, compoundHCID 178418385HCID 178418385, compound

Product 1

HCID 86730359HCID 86730359, compoundYield 43%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Thionyl chloride (118 μL, 1.62 mmol) was added to a solution of benzotriazole (193 mg, 1.62 mmol) in dichloromethane (5 mL) under nitrogen atmosphere at room temperature, and the mixture was stirred for 5 minutes. 4-(1-(tert-Butoxycarbonyl)azetidin-3-yl)benzoic acid described in Production Example 26-5 (300 mg, 1.08 mmol) was added to the reaction liquid, and the mixture was further stirred for 1 hour. The reaction liquid was filtered through anhydrous sodium sulfate on the glass filter, and the resultant was washed with dichloromethane. A solution of triethylamine (748 μL, 5.40 mmol), 4-dimethylaminopyridine (6.60 mg, 0.054 mmol), and 5-((2-aminopyridin-4-yl)oxy)-6-(3-methoxypropoxy)-N-methyl-1H-indole-1-carboxamide described in Production Example 32-8 (200 mg, 0.54 mmol) in tetrahydrofuran (10 mL) was added to the resultant dichloromethane solution under nitrogen atmosphere at 0° C., and the mixture was stirred for 4 hours and 20 minutes. The reaction liquid was diluted with ethyl acetate and water. The organic layer was washed with a saturated saline solution and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration and then the filtrate was concentrated under vacuum. Tetrahydrofuran and an excessive quantity of methylamine tetrahydrofuran solution were added to the residue, and the mixture was stirred at room temperature. The liquid mixture was concentrated under vacuum. The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=2:3-0:1) to obtain the title compound (146 mg, 43%).

Workup

  1. additionwas added to the reaction liquid
  2. stirringthe mixture was further stirred for 1 hour
  3. customThe reaction liquid
  4. filtrationwas filtered through anhydrous sodium sulfate on the glass
  5. filtrationfilter
  6. washthe resultant was washed with dichloromethane
  7. stirringthe mixture was stirred for 4 hours and 20 minutes
  8. customThe reaction liquid
  9. washThe organic layer was washed with a saturated saline solution
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe drying agent was separated by filtration
  12. concentrationthe filtrate was concentrated under vacuum
  13. additionTetrahydrofuran and an excessive quantity of methylamine tetrahydrofuran solution were added to the residue
  14. stirringthe mixture was stirred at room temperature
  15. concentrationThe liquid mixture was concentrated under vacuum
  16. customThe residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=2:3-0:1)

Sources & evidence

ORD record
ord-24b511cd2916404998dc119113f18f65
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Reaction notes

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