Triethylamine → (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 hydrochloride

HRID 1943221

反応式

HRID 1943221 の反応式
[ClH:1].Cl.[S:3]1[C:7]2[CH:8]=[CH:9][C:10]([CH2:12][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)=[CH:11][C:6]=2[N:5]=[N:4]1.C(N(CC)CC)C.S1C2C=CC(C=O)=CC=2N=N1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO>[ClH:1].[S:3]1[C:7]2[CH:8]=[CH:9][C:10]([CH2:12][NH:13][CH:14]3[CH2:15][CH2:16][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)[CH2:18][CH2:19]3)=[CH:11][C:6]=2[N:5]=[N:4]1

参加物

8

反応物 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 185046971,2,3-Benzothiadiazole-5-carbaldehydeHCID 68598460HCID 68598460、化合物

生成物 1

HCID 68598402(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 hydrochloride収率 36%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6212Chloroform溶媒

実験手順

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)) (60 mg, 0.161 mmol) in chloroform (2 ml) and methanol (0.100 ml) at rt under nitrogen was treated with triethylamine (0.067 ml, 0.482 mmol) and stirred at rt for 15 h. The solution was then treated with 1,2,3-benzothiadiazole-5-carbaldehyde (for a synthesis see WO0208224 Example 20(a)) (23.75 mg, 0.145 mmol) and stirred for a further 30 min. The solution was then treated with sodium triacetoxyborohydride (102 mg, 0.482 mmol) and stirred at rt for 45 min, LC-MS after 45 min showed reaction complete. This was then treated with saturated aqueous NaHCO3 (10 ml) and extracted with 20% methanol/DCM (3×25 ml). The combined organic extracts were dried (MgSO4), filtered, evaporated and chromatographed (0-5% methanol/DCM 5% methanol/DCM) to give the free base of the title compound (26 mg, 36%) as a pale yellow solid.

後処理

  1. stirringstirred for a further 30 min
  2. stirringstirred at rt for 45 min
  3. waitLC-MS after 45 min showed
  4. customreaction complete
  5. extractionextracted with 20% methanol/DCM (3×25 ml)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customchromatographed (0-5% methanol/DCM 5% methanol/DCM)

出典と根拠

ORDレコード
ord-acee265a350b428d83706cc55ad05059
出典データセット
uspto-grants-2013_03
特許番号
US08389524B2

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