Chloroform → (1R)-1-({4-Methyl-4-[([1,3]oxathiolo[5,4-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 1943208Notes

Reaction equation

HRID 1943208 reaction equation
[NH2:1][C:2]1([CH3:23])[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.[S:24]1[C:32]2[CH:31]=[C:30]([CH:33]=O)[N:29]=[CH:28][C:27]=2[O:26][CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].C(Cl)(Cl)[Cl:55]>CO>[ClH:55].[CH3:23][C:2]1([NH:1][CH2:33][C:30]2[N:29]=[CH:28][C:27]3[O:26][CH2:25][S:24][C:32]=3[CH:31]=2)[CH2:3][CH2:4][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)[CH2:6][CH2:7]1

Participants

7

Reactant 5

HCID 6212ChloroformHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59254367[1,3]Oxathiolo[5,4-c]pyridine-6-carbaldehydeHCID 68595973(1R)-1-[(4-Amino-4-methyl-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione

Product 1

HCID 68598707(1R)-1-({4-Methyl-4-[([1,3]oxathiolo[5,4-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 75%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of (1R)-1-[(4-amino-4-methyl-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione (26 mg, 0.083 mmol) (for a preparation see Example 23(i)) in chloroform (2 ml) and methanol (0.1 ml) at rt under argon was treated with [1,3]oxathiolo[5,4-c]pyridine-6-carbaldehyde (13.83 mg, 0.083 mmol) (for a synthesis see WO2004058144 Example 61) and stirred at rt for 2 h. The solution was then treated with sodium triacetoxyborohydride (52.6 mg, 0.248 mmol) and stirred at rt for 0.5 h. The reaction was then treated with saturated aqueous NaHCO3 (10 ml) and extracted with 20% methanol/DCM (3×50 ml). The combined organic fractions were dried (MgSO4), filtered, evaporated and chromatographed (0-20% methanol/DCM, Rf=0.3 in 15% methanol/DCM) to give the free base of the title compound as a yellow solid (29 mg, 75%,).

Workup

  1. stirringstirred at rt for 0.5 h
  2. extractionextracted with 20% methanol/DCM (3×50 ml)
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customchromatographed (0-20% methanol/DCM, Rf=0.3 in 15% methanol/DCM)

Sources & evidence

ORD record
ord-2f486dc0d6e44af7a3c985616ddfef6d
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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