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

반응식

HRID 1943221 반응식
[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

참가 물질

8

반응물 5

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

생성물 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 hydrochloride수율 36%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6212Chloroform용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-acee265a350b428d83706cc55ad05059
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389524B2

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