1-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one → N-(5-cyano-4-(2-methoxyethoxy)pyridin-2-yl)-7-(dimethoxymethyl)-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777964노트

반응식

HRID 1777964 반응식
[CH3:1][O:2][CH:3]([O:23][CH3:24])[C:4]1[C:13]([CH2:14][N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][C:16]2=[O:22])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1.C1([O:31][C:32](=O)[NH:33][C:34]2[CH:39]=[C:38]([O:40][CH2:41][CH2:42][O:43][CH3:44])[C:37]([C:45]#[N:46])=[CH:36][N:35]=2)C=CC=CC=1>CN(C1C=CN=CC=1)C.CC(N(C)C)=O>[C:45]([C:37]1[C:38]([O:40][CH2:41][CH2:42][O:43][CH3:44])=[CH:39][C:34]([NH:33][C:32]([N:7]2[C:6]3[C:11](=[CH:12][C:13]([CH2:14][N:15]4[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][C:16]4=[O:22])=[C:4]([CH:3]([O:23][CH3:24])[O:2][CH3:1])[N:5]=3)[CH2:10][CH2:9][CH2:8]2)=[O:31])=[N:35][CH:36]=1)#[N:46]

참가 물질

5

반응물 2

HCID 1180366581-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one2회HCID 125470569Phenyl (5-cyano-4-(2-methoxyethoxy)pyridin-2-yl)carbamate2회

생성물 1

HCID 118037496N-(5-cyano-4-(2-methoxyethoxy)pyridin-2-yl)-7-(dimethoxymethyl)-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 31374Dimethylacetamide용매

반응 조건

온도
90 °C

실험 절차

A mixture of 1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one (intermediate 81, 1.03 g, 3.08 mmol), phenyl(5-cyano-4-(2-methoxyethoxyl)pyridin-2-yl)carbamate (intermediate 108, 2.19 g, 6.16 mmol) and DMAP (753 mg, 6.16 mmol) in DMA (15 ml) was heated at 90° C. for 3.5 h. The cooled reaction mixture was partitioned between EtOAc and, the organic layer dried over MgSO4 and evaporated. The residue was purified by reversed phase chromatography (RP 4) and the product containing fractions were partitioned between saturated aqueous NaHCO3 and EtOAc, the organic layer dried over MgSO4 and vaporated. The residue was then triturated with a mixture of DCM, Et2O and heptane to give the title compound as a white solid. (UPLC-MS 7) tR 0.80; ESI-MS 554.4 [M+H]+.

후처리

  1. customThe cooled reaction mixture
  2. customwas partitioned between EtOAc
  3. dry with materialthe organic layer dried over MgSO4
  4. customevaporated
  5. customThe residue was purified by reversed phase chromatography (RP 4)
  6. additionthe product containing fractions
  7. customwere partitioned between saturated aqueous NaHCO3 and EtOAc
  8. dry with materialthe organic layer dried over MgSO4
  9. customThe residue was then triturated with a mixture of DCM, Et2O and heptane

출처 및 근거

ORD 기록
ord-81ac7cf972894f90a81c4c4cc7da1838
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09266883B2

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