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

HRID 1778057노트

반응식

HRID 1778057 반응식
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.[CH3:33][N:34]1[C:38](B(O)O)=[CH:37][CH:36]=[N:35]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:38]4[N:34]([CH3:33])[N:35]=[CH:36][CH:37]=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]

참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 11182610(1-methyl-1H-pyrazol-5-yl)boronic acid2회HCID 1180366576-bromo-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2회

생성물 1

HCID 118036911N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 962Water용매HCID 6344Dichloromethane용매HCID 80711,2-Dimethoxyethane용매

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온도
120 °C

실험 절차

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, 50.9 mg, 0.101 mmol), 1-methylpyrazole-5-boronic acid pinacolester (23.9 mg, 0.111 mmol), PdCl2(dppf) (8 mg, 10.93 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. Additional 1-methylpyrazole-5-boronic acid pinacolester (10 mg, 0.047 mmol) and PdCl2(dppf) (8 mg, 10.93 μmol) were added and the reaction mixture was stirred in microwave for 15 min at 120° C. 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 containing fractions were combined, evaporated and dried to yield the title compound as a yellow film. (UPLC-MS 3) tR 0.98 min; ESI-MS 507.2 [M+H]+.

후처리

  1. customwas sealed in a vial and
  2. custompurged with argon
  3. customThen reaction mixture
  4. stirringthe reaction mixture was stirred in microwave for 15 min at 120° C
  5. customwere separated
  6. extractionthe aqueous layer was extracted with DCM
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by silica gel column chromatography
  11. washeluting with a gradient of MeOH (1-5%) in DCM
  12. additionProduct containing fractions
  13. customevaporated
  14. customdried

출처 및 근거

ORD 기록
ord-447186d10a9b40d9a26234ac8bc0825e
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09266883B2

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