Potassium Carbonate → 6'-(5-Chloropyridin-3-yl)-4,4-difluoro-5''-methyl-3'H-dispiro[cyclo hexane-1,2'-indene-1',2''-imidazol]-4''-amine

HRID 539344

反応式

HRID 539344 の反応式
CC([PH+](C(C)(C)C)CCCS([O-])(=O)=O)(C)C.Br[C:18]1[CH:39]=[C:38]2[C:21]([CH2:22][C:23]3([C:31]42[N:35]=[C:34]([NH2:36])[C:33]([CH3:37])=[N:32]4)[CH2:28][CH2:27][C:26]([F:30])([F:29])[CH2:25][CH2:24]3)=[CH:20][CH:19]=1.[Cl:40][C:41]1[CH:42]=[C:43](B(O)O)[CH:44]=[N:45][CH:46]=1.C([O-])([O-])=O.[K+].[K+]>CC1CCCO1.[Na+].[Na+].Cl[Pd+2](Cl)(Cl)Cl.O>[Cl:40][C:41]1[CH:42]=[C:43]([C:18]2[CH:39]=[C:38]3[C:21]([CH2:22][C:23]4([C:31]53[N:35]=[C:34]([NH2:36])[C:33]([CH3:37])=[N:32]5)[CH2:24][CH2:25][C:26]([F:30])([F:29])[CH2:27][CH2:28]4)=[CH:20][CH:19]=2)[CH:44]=[N:45][CH:46]=1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 201118775-Chloropyridine-3-boronic acid2 回HCID 249491873-(Di-tert-butylphosphonium)propane sulfonate2 回HCID 573858836'-Bromo-4,4-difluoro-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine

生成物 1

HCID 573861496'-(5-Chloropyridin-3-yl)-4,4-difluoro-5''-methyl-3'H-dispiro[cyclo hexane-1,2'-indene-1',2''-imidazol]-4''-amine収率 38%

試薬・触媒・溶媒 3

HCID 178479786HCID 178479786、化合物触媒2 回HCID 962Water溶媒HCID 73012-Methyltetrahydrofuran溶媒

反応条件

温度
100 °C

実験手順

Sodium tetrachloropalladate(II) (7.70 mg, 0.03 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (7.02 mg, 0.03 mmol), 6′-bromo-4,4-difluoro-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine (Example 27, 100 mg, 0.26 mmol) and 5-chloropyridin-3-ylboronic acid (52.0 mg, 0.31 mmol) were added to a microwave vial and dissolved in 2-methyl-tetrahydrofuran (1 mL). K2CO3 (2M aq) (0.392 mL, 0.78 mmol) was added and the vial was flushed with Ar (g) and capped. The mixture was heated in a microwave reactor at 100° C. for 45 min. Additional sodium tetrachloropalladate(II) (7.70 mg, 0.03 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (7.02 mg, 0.03 mmol) and 0.5 equiv. 5-chloropyridin-3-ylboronic acid was added to the reaction mixture and it was heated to 90° C. for 1 h. Water was added and the residue was extracted with EtOAc (×3). The organic phases were dried with MgSO4 and concentrated. The crude product was purified on a silica gel column (4 g SiO2, 7 M NH3 in MeOH in DCM 1:9/DCM 0-100%) to give the title compound (41 mg, 38% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.23-1.32 (m, 1 H), 1.52 (br. s., 2 H), 1.72 (br. s., 1 H), 1.79-1.98 (m, 4 H), 2.19 (s, 3 H), 3.08 (d, 1 H), 3.16 (d, 1 H), 6.62 (br. s., 2 H), 6.90 (d, 1 H), 7.43 (d, 1 H), 7.60 (dd, 1 H), 8.10 (t, 1 H), 8.57 (d, 1 H), 8.72 (d, 1 H). MS (APCI+) m/z 415.2 [M+H]+.

後処理

  1. customthe vial was flushed with Ar (g)
  2. customcapped
  3. temperaturewas heated to 90° C. for 1 h
  4. extractionthe residue was extracted with EtOAc (×3)
  5. dry with materialThe organic phases were dried with MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified on a silica gel column (4 g SiO2, 7 M NH3 in MeOH in DCM 1:9/DCM 0-100%)

出典と根拠

ORDレコード
ord-5894770a13fd4214bf2522d33ca48035
出典データセット
uspto-grants-2014_10
特許番号
US08865911B2

関連ノート

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