Triethylamine → HCID 68600762, compound

HRID 1943215Notes

Reaction equation

HRID 1943215 reaction equation
[ClH:1].Cl.S1C2C=CC(C[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH2:20][C@H:21]4[N:31]5[C:32]6[N:23]([C:24](=[O:34])[CH:25]=[CH:26][C:27]=6[CH:28]=[CH:29][C:30]5=[O:33])[CH2:22]4)[CH2:16][CH2:15]3)=CC=2N=N1.C(N(CC)CC)C.[F:42][C:43]1[C:48]2[O:49][CH2:50][CH2:51][O:52][C:47]=2[CH:46]=[C:45]([CH:53]=O)[CH:44]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO>[ClH:1].[F:42][C:43]1[C:48]2[O:49][CH2:50][CH2:51][O:52][C:47]=2[CH:46]=[C:45]([CH2:53][NH:13][CH:14]2[CH2:15][CH2:16][N:17]([CH2:20][C@H:21]3[N:31]4[C:32]5[N:23]([C:24](=[O:34])[CH:25]=[CH:26][C:27]=5[CH:28]=[CH:29][C:30]4=[O:33])[CH2:22]3)[CH2:18][CH2:19]2)[CH:44]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 574231098-Fluoro-2,3-dihydro-1,4-benzodioxin-6-carboxaldehydeHCID 68598460HCID 68598460, compound

Product 1

HCID 68600762HCID 68600762, compoundYield 9.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A suspension of (1R)-1-({4-[(1,2,3-benzothiadiazol-5-ylmethyl)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)) (50 mg, 0.134 mmol) in chloroform (2 ml) and methanol (0.100 ml) at rt under argon was treated with triethylamine (0.056 ml, 0.402 mmol) and stirred at rt for 15 min. The solution was then treated with 8-fluoro-2,3-dihydro-1,4-benzodioxin-6-carbaldehyde (for a synthesis see WO2007122258, Example 8(b)) (21.96 mg, 0.121 mmol) and stirred for a further 30 min. The solution was treated with sodium triacetoxyborohydride (85 mg, 0.402 mmol) and stirred at rt for 30 min, LCMS after 30 min showed there was still starting material and the imine of the product. So more sodium triacetoxyborohydride (40 mg) was added, the reaction was stirred for a further 30 min. LCMS after this time showed that the reaction was complete. The reaction was then treated with saturated aqueous NaHCO3 (10 ml) and extracted with 20% methanol/DCM (3×25 ml). The combined organic fractions were dried (MgSO4), filtered, evaporated and chromatographed (0-20% methanol/DCM) to give the free base of the title compound (6 mg, 9.6%) as a pale yellow solid and some crude product (15 mg, 24%) as an impure pale yellow solid which was purified using an SCX column to give more identical title compound, free base.

Workup

  1. stirringstirred for a further 30 min
  2. stirringstirred at rt for 30 min
  3. waitLCMS after 30 min showed
  4. stirringthe reaction was stirred for a further 30 min
  5. extractionextracted with 20% methanol/DCM (3×25 ml)
  6. dry with materialThe combined organic fractions were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customchromatographed (0-20% methanol/DCM)

Sources & evidence

ORD record
ord-40310a2399374d228689833012f64351
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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