Triethylamine → (1R)-1-({4-[(6,7-Dihydro-5H-cyclopenta[c]pyridin-3-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride

HRID 1943164ノート

反応式

HRID 1943164 の反応式
[ClH:1].Cl.[NH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][C@H:11]2[N:21]3[C:22]4[N:13]([C:14](=[O:24])[CH:15]=[CH:16][C:17]=4[CH:18]=[CH:19][C:20]3=[O:23])[CH2:12]2)[CH2:6][CH2:5]1.C(N(CC)CC)C.[CH:32]1[C:37]2[CH2:38][CH2:39][CH2:40][C:36]=2[CH:35]=[C:34]([CH:41]=O)[N:33]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO>[ClH:1].[CH:32]1[C:37]2[CH2:38][CH2:39][CH2:40][C:36]=2[CH:35]=[C:34]([CH2:41][NH:3][CH:4]2[CH2:5][CH2:6][N:7]([CH2:10][C@H:11]3[N:21]4[C:22]5[N:13]([C:14](=[O:24])[CH:15]=[CH:16][C:17]=5[CH:18]=[CH:19][C:20]4=[O:23])[CH2:12]3)[CH2:8][CH2:9]2)[N:33]=1

参加物

8

反応物 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 66658412(1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochlorideHCID 866420966,7-Dihydro-5H-cyclopenta[c]pyridine-3-carbaldehyde

生成物 1

HCID 68597793(1R)-1-({4-[(6,7-Dihydro-5H-cyclopenta[c]pyridin-3-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride収率 41%

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-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochloride (82 mg, 0.220 mmol) (for a preparation see Example 5(j)) in chloroform (5 ml) and methanol (0.2 ml) at rt under argon was treated with triethylamine (92 μl, 0.659 mmol) and stirred at rt for 0.25 h. The solution was then treated with 6,7-dihydro-5H-cyclopenta[c]pyridine-3-carbaldehyde (32.3 mg, 0.220 mmol) and stirred for a further 0.5 h. The solution was then treated with NaBH(OAc)3 (140 mg, 0.659 mmol) and stirred at rt for 0.5 h. The reaction was then treated with saturated aqueous NaHCO3 (100 ml) and extracted with 20% methanol/DCM (3×200 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 (39 mg, 41%).

後処理

  1. stirringstirred for a further 0.5 h
  2. stirringstirred at rt for 0.5 h
  3. extractionextracted with 20% methanol/DCM (3×200 ml)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customchromatographed (0-20% methanol/DCM)

出典と根拠

ORDレコード
ord-cce975f95a7c4eaaa8be183fe2330409
出典データセット
uspto-grants-2013_03
特許番号
US08389524B2

反応ノート

読み込み中…