Sodium Carbonate → HCID 70872426、化合物

HRID 1530323ノート

反応式

HRID 1530323 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH3:17][C:18]1[CH:23]=[C:22]([CH3:24])[NH:21][C:20](=[O:25])[C:19]=1[CH2:26][NH:27][C:28](=[O:54])[C:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[C:31]([N:44]([CH2:51][CH3:52])[CH:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)[C:30]=1[CH3:53].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:7]([C:6]1[CH:9]=[C:2]([C:33]2[CH:32]=[C:31]([N:44]([CH2:51][CH3:52])[CH:45]3[CH2:50][CH2:49][O:48][CH2:47][CH2:46]3)[C:30]([CH3:53])=[C:29]([C:28]([NH:27][CH2:26][C:19]3[C:20](=[O:25])[NH:21][C:22]([CH3:24])=[CH:23][C:18]=3[CH3:17])=[O:54])[CH:34]=2)[CH:3]=[CH:4][C:5]=1[CH2:10][N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)#[N:8]

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 59558570HCID 59558570、化合物HCID 70872817HCID 70872817、化合物

生成物 1

HCID 70872426HCID 70872426、化合物収率 6%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a stirred solution of 5-bromo-2-(morpholinomethyl)benzonitrile (190 mg, 0.68 mmol) and N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (200 mg, 0.45 mmol) in dioxane (6 mL), aqueous 2M Na2CO3 solution (0.81 mL, 1.63 mmol) was added and solution was purged with argon for 15 min. Then Pd(PPh3)4 (52 mg, 0.04 mmol) was added and argon was purged again for 15 min. Reaction mass was heated at 100° C. for 4 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM (3 times). Combined organic layer was dried over sodium sulphate. Removal of the solvent under reduced pressure followed by column chromatographic purification afforded the title compound (16 mg, 6%). LCMS: 598.20 (M+1)+; HPLC: 89/15% (@254 nm) (Rt; 4.039; Method: Column: YMC ODS-A 150 mm×4.6 mm×5μ; Mobile Phase; A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 μL, Col. Temp.: 30° C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) δ 11.46 (bs, 1H), 8.20 (t, 1H), 8.15 (s, 1H), 7.94 (d, 1H, J=6.8 Hz), 7.63 (d, 1H, J=8.4 Hz), 7.51 (s, 1H), 7.31 (s, 1H), 5.86 (s, 1H), 4.29 (m, 2H), 3.84-3.82 (m, 2H), 3.66-3.58 (m, 6H), 3.32 (m, 5H), 3.11-3.03 (m, 4H), 2.25 (s, 3H), 2.21 (s, 3H), 2.11 (s, 3H), 1.65-1.51 (m, 4H), 0.82 (t, 3H, J=6 Hz).

後処理

  1. customsolution was purged with argon for 15 min
  2. customargon was purged again for 15 min
  3. customReaction mass
  4. customOn completion, reaction mixture
  5. extractionextracted with 10% MeOH/DCM (3 times)
  6. dry with materialCombined organic layer was dried over sodium sulphate
  7. customRemoval of the solvent under reduced pressure
  8. customfollowed by column chromatographic purification

出典と根拠

ORDレコード
ord-76a67f5e6faf4eab819a131c92994c1b
出典データセット
uspto-grants-2015_07
特許番号
US09090562B2

反応ノート

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