Potassium Carbonate → 4-[1-cyano-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-benzoic acid tert-butyl ester

HRID 1773914

반응식

HRID 1773914 반응식
I[C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:3]=1[C:24]#[N:25].[C:26]([O:30][C:31](=[O:47])[C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:33]=1)([CH3:29])([CH3:28])[CH3:27].C([O-])([O-])=O.[K+].[K+]>C1COCC1.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:26]([O:30][C:31](=[O:47])[C:32]1[CH:37]=[CH:36][C:35]([C:2]2[N:11]=[C:10]3[N:4]([CH2:5][CH2:6][C:7]4[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=4[CH:9]3[O:12][CH:13]3[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH2:18]3)[C:3]=2[C:24]#[N:25])=[CH:34][CH:33]=1)([CH3:29])([CH3:27])[CH3:28]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 43767661,1-Dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 867039962-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carbonitrile

생성물 1

HCID 867039954-[1-cyano-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-benzoic acid tert-butyl ester

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8028Tetrahydrofuran용매

반응 조건

온도
85 °C

실험 절차

To a solution of 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carbonitrile (example 221) (215 mg, 0.48 mmole) in THF (3 mL) are added 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid tert-butyl ester (191 mg, 0.63 mmole), 1M aqueous K2CO3 (2 mL) and PdCl2(dppf)2 (20 mg). The flask is evacuated and filled with argon. The reaction mixture is heated at 85° C. for 24 hours. AcOEt is added and the organic phase is washed with water, dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH) (100:0) to (95:5) to give 4-[1-cyano-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-benzoic acid tert-butyl ester melting at 95° C.

후처리

  1. customThe flask is evacuated
  2. additionfilled with argon
  3. additionAcOEt is added
  4. washthe organic phase is washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customThe residue is purified by silica gel chromatography
  9. washeluting with (CH2Cl2:MeOH) (100:0) to (95:5)

출처 및 근거

ORD 기록
ord-6cd14e08c47b48af9bfa6f9c25617101
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09255101B2

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