Triethylamine → HCID 68598080, compound

HRID 1943236Notes

Reaction equation

HRID 1943236 reaction equation
[ClH:1].Cl.[NH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][C@H:11]2[N:21]3[C:22]4[N:13]([C:14](=[O:24])[CH:15]=[CH:16][C:17]=4[CH:18]=[CH:19][C:20]3=[O:23])[CH2:12]2)[CH2:6][CH2:5]1.C(N(CC)CC)C.[O:32]1[C:41]2[C:36](=[CH:37][C:38]([CH:42]=O)=[CH:39][CH:40]=2)[CH2:35][CH2:34][CH2:33]1.NC1CCN(C[C@H]2N3C4N(C(=O)C=CC=4C=CC3=O)C2)CC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO.C(=O)(O)[O-].[Na+]>[ClH:1].[O:32]1[C:41]2[C:36](=[CH:37][C:38]([CH2:42][NH:3][CH:4]3[CH2:5][CH2:6][N:7]([CH2:10][C@H:11]4[N:21]5[C:22]6[N:13]([C:14](=[O:24])[CH:15]=[CH:16][C:17]=6[CH:18]=[CH:19][C:20]5=[O:23])[CH2:12]4)[CH2:8][CH2:9]3)=[CH:39][CH:40]=2)[CH2:35][CH2:34][CH2:33]1

Participants

9

Reactant 5

HCID 8471Triethylamine2×HCID 5049666Sodium triacetoxyborohydrideHCID 6504215Chroman-6-carbaldehydeHCID 58001796(1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dioneHCID 66658412(1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochloride

Product 1

HCID 68598080HCID 68598080, compoundYield 22%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

A solution of (1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochloride (for a preparation see Example 5A(j)) (12 mg, 0.032 mmol) and triethylamine (0.139 ml, 0.999 mmol) in DCM (4.5 ml) and methanol (0.5 ml) at rt was stirred for 5 min. 3,4-Dihydro-2H-chromene-6-carbaldehyde (commercially available) (45 mg, 0.277 mmol) was added and the resulting solution was stirred overnight for 18 h. LCMS showed that aldehyde remained and no amine remained. Additional (1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione (120 mg, 0.321 mmol) and additional triethylamine (0.138 ml, 0.999 mmol) were added and the resulting mixture stirred for 1 h. Additional sodium triacetoxyborohydride (294 mg, 1.387 mmol) was added and resulting solution was stirred for 60 h. The reaction was diluted with DCM (10 ml) and sodium bicarbonate solution (10 ml) and stirred at rt for 10 mins and extracted with methanol:DCM (20%, 3×150 ml). The combined organic extracts were dried (MgSO4), filtered, evaporated and chromatographed (0-50% methanol:DCM). The column waste was concentrated to afford a brown oil that was re-chromatographed (0-50% methanol:DCM). The relevant fractions were combined to afford the free base of the title compound as a white solid (27 mg, 0.06 mmol, 22%).

Workup

  1. customat rt
  2. stirringthe resulting solution was stirred overnight for 18 h
  3. stirringthe resulting mixture stirred for 1 h
  4. customresulting solution
  5. stirringwas stirred for 60 h
  6. stirringstirred at rt for 10 mins
  7. extractionextracted with methanol
  8. dry with materialThe combined organic extracts were dried (MgSO4)
  9. filtrationfiltered
  10. customevaporated
  11. customchromatographed (0-50% methanol:DCM)
  12. concentrationThe column waste was concentrated
  13. customto afford a brown oil that
  14. customwas re-chromatographed (0-50% methanol:DCM)

Sources & evidence

ORD record
ord-38c84a4d4d4b4947855111ce556ee67e
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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