Acetic Acid → HCID 10308735, compound

HRID 1624351Notes

Reaction equation

HRID 1624351 reaction equation
C(OC([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:17][NH:18][CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1)=O)(C)(C)C.C(OC(=O)[NH:35][CH2:36][CH2:37][CH:38]=O)(C)(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>C1COCC1>[NH:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:17][N:18]([CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1)[CH2:38][CH2:37][CH2:36][NH2:35]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 10910051tert-Butyl N-(3-oxopropyl)carbamateHCID 219850812-[(5,6,7,8-Tetrahydroquinolin-8-ylamino)-methyl]-benzimidazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 10308735HCID 10308735, compoundYield 88.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-[(5,6,7,8-tetrahydro-quinolin-8-ylamino)-methyl]-benzoimidazole-1-carboxylic acid tert-butyl ester (390 mg, 0.98 mmol), (3-oxo-propyl)-carbamic acid tert-butyl ester (170 mg, 0.98 mmol) from above and THF (9.8 mL) was added NaBH(OAc)3 (623 mg, 2.94 mmol) and the resulting mixture was stirred at room temperature for 1 hour. AcOH (56 μL, 0.98 mmol) was added and the mixture stirred at room temperature overnight. The mixture was concentrated under reduced pressure, diluted with CH2Cl2 (40 mL) and washed with 1N NaOH (10 mL). The aqueous was extracted with (2×20 mL) and the combined organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure. A solution of the resulting orange foam in CH2Cl2 (4 mL) and TFA (4 mL) was stirred at room temperature for 2.5 hours. The mixture was concentrated under reduced pressure, partially dissolved in H2O (2 mL), basified with 1N NaOH and extracted with CH2Cl2 (3×25 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure. Purification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 100:7:1) afforded N1-(1H-benzoimidazol-2-ylmethyl)-N1-(5,6,7,8-tetrahydro-quinolin-8-yl)-propane-1,3-diamine (290 mg, 75% over 3 steps) as a white foam.

Workup

  1. stirringthe mixture stirred at room temperature overnight
  2. concentrationThe mixture was concentrated under reduced pressure
  3. additiondiluted with CH2Cl2 (40 mL)
  4. washwashed with 1N NaOH (10 mL)
  5. extractionThe aqueous was extracted with (2×20 mL)
  6. dry with materialthe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. stirringA solution of the resulting orange foam in CH2Cl2 (4 mL) and TFA (4 mL) was stirred at room temperature for 2.5 hours
  10. concentrationThe mixture was concentrated under reduced pressure
  11. dissolutionpartially dissolved in H2O (2 mL)
  12. extractionextracted with CH2Cl2 (3×25 mL)
  13. dry with materialThe combined organic extracts were dried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customPurification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 100:7:1)

Sources & evidence

ORD record
ord-0dd0e9e6f10f4257a667cf08f284e7d9
Source dataset
uspto-grants-2014_07
Patent number
US08778967B2

Reaction notes

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