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

HRID 1943160노트

반응식

HRID 1943160 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:41]2[CH2:40][CH2:39][CH2:38][CH2:37][C:36]=2[CH:35]=[C:34]([CH:42]=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:41]2[CH2:40][CH2:39][CH2:38][CH2:37][C:36]=2[CH:35]=[C:34]([CH2:42][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 187995785,6,7,8-Tetrahydroisoquinoline-3-carbaldehydeHCID 66658412(1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochloride

생성물 1

HCID 68597352(1R)-1-({4-[(5,6,7,8-Tetrahydro-3-isoquinolinylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride수율 64%

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 (87 mg, 0.233 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 (970.699 mmol) and stirred at rt for 0.25 h. The solution was then treated with 5,6,7,8-tetrahydro-3-isoquinolinecarbaldehyde (37.6 mg, 0.233 mmol) and stirred for a further 0.5 h. The solution was then treated with NaBH(OAc)3 (148 mg, 0.699 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 (66 mg, 64%).

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-a89d561d43554f21ba69f7cad1a2e4fc
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389524B2

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