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

HRID 1943235노트

반응식

HRID 1943235 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.[O:32]1[C:36]2[CH:37]=[C:38]([CH:41]=O)[CH:39]=[CH:40][C:35]=2[CH2:34][CH2:33]1>C(Cl)(Cl)Cl.CO>[ClH:1].[O:32]1[C:36]2[CH:37]=[C:38]([CH2:41][NH:3][CH:4]3[CH2:5][CH2:6][N:7]([CH2:10][C@H:11]4[N:21]5[C:22]6[N:13]([C:14](=[O:24])[CH:15]=[CH:16][C:17]=6[CH:18]=[CH:19][C:20]5=[O:23])[CH2:12]4)[CH2:8][CH2:9]3)[CH:39]=[CH:40][C:35]=2[CH2:34][CH2:33]1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 149643942,3-Dihydrobenzofuran-6-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 68598338(1R)-1-({4-[(2,3-Dihydro-1-benzofuran-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride수율 26%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6212Chloroform용매2회

실험 절차

A solution 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 (for a preparation see Example 5A(j)) (133 mg, 0.356 mmol) and triethylamine (0.124 ml, 0.891 mmol) in chloroform (4.5 ml) and methanol (0.5 ml) at rt was stirred at rt for 15 min then 2,3-dihydro-1-benzofuran-6-carbaldehyde (44 mg, 0.297 mmol) in chloroform (2 ml) was added dropwise at rt. The reaction mixture was stirred at rt overnight. The reaction was quenched with NaHCO3 (aq) (20 ml), extracted with 20% MeOH/DCM (3×30 ml). The combined organic layers were dried over MgSO4, filtered, evaporated and chromatographed (0-50% MeOH/DCM). The relevant fractions were combined and evaporated to deliver the free base of the title compound as a pale yellow clear oil (18 mg, 0.04 mmol, 26%).

후처리

  1. customat rt
  2. stirringThe reaction mixture was stirred at rt overnight
  3. customThe reaction was quenched with NaHCO3 (aq) (20 ml)
  4. extractionextracted with 20% MeOH/DCM (3×30 ml)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customchromatographed (0-50% MeOH/DCM)
  9. customevaporated

출처 및 근거

ORD 기록
ord-07954d12bd794a9588c265d122c3dcf0
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389524B2

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