Sodium Carbonate → N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(pyridin-3-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1778056ノート

反応式

HRID 1778056 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:15][CH3:16])[O:13][CH3:14])[N:8]([C:17]([NH:19][C:20]1[CH:25]=[C:24]([NH:26][CH2:27][CH2:28][O:29][CH3:30])[C:23]([C:31]#[N:32])=[CH:22][N:21]=1)=[O:18])[CH2:7][CH2:6][CH2:5]2.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35](B(O)O)[CH:34]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C(Cl)Cl.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:31]([C:23]1[C:24]([NH:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:25][C:20]([NH:19][C:17]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([C:35]4[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=4)=[C:11]([CH:12]([O:15][CH3:16])[O:13][CH3:14])[N:10]=3)[CH2:5][CH2:6][CH2:7]2)=[O:18])=[N:21][CH:22]=1)#[N:32]

参加物

8

反応物 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 1180366576-bromo-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2 回

生成物 1

HCID 118036908N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(pyridin-3-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
120 °C

実験手順

A suspension of 6-bromo-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 315, 49.9 mg, 0.099 mmol), 3-pyridineboronic acid (14 mg, 0.108 mmol), PdCl2(dppf) (7 mg, 9.57 μmol) and saturated aqueous Na2CO3 (160 μl) in DME (480 μl) was sealed in a vial and purged with argon. Then reaction mixture was stirred at 120° C. for 15 min in a microwave. The suspension was diluted with DCM and water, phases were separated and the aqueous layer was extracted with DCM. The organic layers were combined, dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (1-5%) in DCM. Product fractions were combined, evaporated and dried to yield the title compound as a colorless film. (UPLC-MS 3) tR 0.97 min; ESI-MS 504.2 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 8.66-8.62 (m, 2H), 8.22 (s, 1H), 7.83 (dt, 1H), 7.59 (s, 1H), 7.43 (s, 1H), 7.40 (d d, 1H), 5.34 (s, 1H), 5.24 (t, 1H), 4.11-4.06 (m, 2H), 3.63 (t, 2H), 3.48 (q, 2H), 3.42-3.36 (m, 9H), 2.90 (t, 2H), 2.04 (q, 2H).

後処理

  1. customwas sealed in a vial and
  2. custompurged with argon
  3. customThen reaction mixture
  4. customwere separated
  5. extractionthe aqueous layer was extracted with DCM
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by silica gel column chromatography
  10. washeluting with a gradient of MeOH (1-5%) in DCM
  11. customevaporated
  12. customdried

出典と根拠

ORDレコード
ord-44664f4586dc4419ad82774f1551fb24
出典データセット
uspto-grants-2016_02
特許番号
US09266883B2

反応ノート

読み込み中…