Sodium Bicarbonate → 7-[({1-[(4,9-Dioxo-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridin-1-yl)methyl]-4-piperidinyl}amino)methyl]-2,3-dihydro-1,4-benzodioxin-5-carbonitrile hydrochloride

HRID 1943171Notes

Reaction equation

HRID 1943171 reaction equation
[O:1]=[C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH2:7][C:6](=[O:12])[N:5]3[CH2:13][CH:14]([CH2:15][N:16]4[CH2:21][CH2:20][CH:19]([NH:22]C(=O)OC(C)(C)C)[CH2:18][CH2:17]4)[N:3]1[C:4]=23.[CH:30]([C:32]1[CH:33]=[C:34]([C:42]#[N:43])[C:35]2[O:40][CH2:39][CH2:38][O:37][C:36]=2[CH:41]=1)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(=O)(O)[O-].[Na+].[Cl:63]CCl.CO>>[ClH:63].[O:12]=[C:6]1[CH:7]=[CH:8][C:9]2[CH:10]=[CH:11][C:2](=[O:1])[N:3]3[CH:14]([CH2:15][N:16]4[CH2:17][CH2:18][CH:19]([NH:22][CH2:30][C:32]5[CH:33]=[C:34]([C:42]#[N:43])[C:35]6[O:40][CH2:39][CH2:38][O:37][C:36]=6[CH:41]=5)[CH2:20][CH2:21]4)[CH2:13][N:5]1[C:4]=23

Participants

6

Reactant 5

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 21226129Dichloromethane methanolHCID 57423114HCID 57423114, compoundHCID 58001733HCID 58001733, compound

Product 1

HCID 685962937-[({1-[(4,9-Dioxo-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridin-1-yl)methyl]-4-piperidinyl}amino)methyl]-2,3-dihydro-1,4-benzodioxin-5-carbonitrile hydrochlorideYield 27%

Procedure

1-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione (2:1 mixture of R:S) (60 mg, 0.2 mmol) and 7-formyl-2,3-dihydro-1,4-benzodioxin-5-carbonitrile (for a synthesis see WO06014580 Preparation 13 or WO2007122258 Example 31(d)) (37.8 mg, 0.2 mmol) were dissolved in dichloromethane/methanol (2/0.1 ml) at room temperature under argon and stirred at room temperature for 1 h. This was then treated with NaBH(OAc)3 (85 mg, 0.4 mmol) and left to stir for 1 hour. A saturated solution of sodium bicarbonate (15 ml) was then added and the aqueous was extracted with 20% methanol/dichloromethane (3×35 ml). The combined organic extracts were dried on magnesium sulphate, filtered and evaporated. The crude was purified by silica chromatography using a 0-20% methanol/dichloromethane gradient to provide the free base of the title compound as a pale yellow gum (26 mg, 27%).

Workup

  1. waitleft
  2. stirringto stir for 1 hour
  3. extractionthe aqueous was extracted with 20% methanol/dichloromethane (3×35 ml)
  4. customThe combined organic extracts were dried on magnesium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude was purified by silica chromatography

Sources & evidence

ORD record
ord-ab02787be8cb4bf0af51619468d094f2
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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