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 1943164노트

반응식

HRID 1943164 반응식
[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

참가 물질

8

반응물 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

생성물 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 hydrochloride수율 41%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6212Chloroform용매

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-cce975f95a7c4eaaa8be183fe2330409
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389524B2

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