Sodium Bicarbonate → (1R)-1-({4-[(3,4-Dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride

HRID 1943167Notes

Reaction equation

HRID 1943167 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@H:9]2[N:19]3[C:20]4[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=4[CH:16]=[CH:17][C:18]3=[O:21])[CH2:10]2)[CH2:4][CH2:3]1.[O:23]1[C:28]2=[CH:29][N:30]=[C:31]([CH:33]=O)[CH:32]=[C:27]2[CH2:26][CH2:25][CH2:24]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+].C(Cl)(Cl)[Cl:55].CO>C(N(CC)CC)C>[ClH:55].[O:23]1[C:28]2=[CH:29][N:30]=[C:31]([CH2:33][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][C@H:9]4[N:19]5[C:20]6[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=6[CH:16]=[CH:17][C:18]5=[O:21])[CH2:10]4)[CH2:6][CH2:7]3)[CH:32]=[C:27]2[CH2:26][CH2:25][CH2:24]1

Participants

7

Reactant 5

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 21584188Chloroform methanolHCID 566403113,4-dihydro-2H-pyrano[2,3-c]pyridine-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-dione

Product 1

HCID 68596291(1R)-1-({4-[(3,4-Dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochlorideYield 32%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

A suspension of (1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione (for a preparation see Example 5(j)) (51 mg, 0.14 mmol) in chloroform:methanol (9:1, 3 ml) at rt under argon was treated with triethylamine (0.06 ml) and stirred at rt for 10 min. The solution was then treated with 3,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehyde (for a synthesis see WO2004058144, Example 126(e)) (21 mg, 0.133 mmol) and stirred for a further 2 h. The solution was then treated with NaBH(OAc)3 (87 mg) and stirred at rt for 2 h. The reaction was then treated with saturated aqueous NaHCO3 (10 ml) and extracted with 20% methanol/DCM (3×50 ml). The combined organic extracts were dried (MgSO4), filtered, evaporated and chromatographed (0-20% methanol/DCM) to give the free base of the title compound as a light brown solid (20 mg, 32%)

Workup

  1. customat rt
  2. stirringstirred for a further 2 h
  3. stirringstirred at rt for 2 h
  4. extractionextracted with 20% methanol/DCM (3×50 ml)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customchromatographed (0-20% methanol/DCM)

Sources & evidence

ORD record
ord-6afb6e76cfb341f2b48e741a44f0de13
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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