Sodium Carbonate → 3'-Methylene-2',3',6,7,8,9-hexahydrospiro[imidazo[1,5-a]azepine-5,1'-indene]-5'-carbonitrile

HRID 76906ノート

反応式

HRID 76906 の反応式
[CH2:1]([C:4]1([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2Br)[N:10]2[CH:11]=[N:12][CH:13]=[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5]1)[CH:2]=[CH2:3].C(=O)([O-])[O-].[Na+].[Na+].FC1C=CC(B(O)O)=CC=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.COCCOC>[CH2:3]=[C:2]1[C:21]2[C:14](=[CH:15][CH:16]=[C:17]([C:18]#[N:19])[CH:20]=2)[C:4]2([N:10]3[CH:11]=[N:12][CH:13]=[C:9]3[CH2:8][CH2:7][CH2:6][CH2:5]2)[CH2:1]1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 588270494-(5-allyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl)-3-bromobenzonitrile

生成物 1

HCID 588270643'-Methylene-2',3',6,7,8,9-hexahydrospiro[imidazo[1,5-a]azepine-5,1'-indene]-5'-carbonitrile

試薬・触媒・溶媒 2

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
130 °C

実験手順

To 4-(5-allyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl)-3-bromobenzonitrile (0.275 g, 0.76 mmol) is added DME (3.0 mL). To this solution is added aqueous 2M sodium carbonate (1.5 ml, 3.0 mmol) followed by 4-fluorophenylboronic acid (0.269 g, 1.92 mmol). This mixture is transferred to a microwave safe vial Tetrakis(triphenylphosphine) palladium(0) (0.04 g, 0.034 mmol) is added, and the vessel sealed. The mixture is stirred briefly (30 seconds) and place in a microwave for 25 minutes at 130° C. The vial is allowed to cool and unsealed. The mixture is extracted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The separated organic layer is concentrated in vacuo. The resulting material is subjected to two sequential chromatography procedures (1: Silica gel, 1:50 to 1:25 methanol:methylene chloride. 2: Reverse phase HPLC, gradient 10-95% % Acetonitrile:Water, pH2, over 8 minutes) to give the product. MS (ESI) m/z 276 (M+11); 1H NMR (400 MHz, CDCl3) δ ppm 1.47-1.61 (m, 1H), 1.85-1.99 (m, 1H), 2.01-2.16 (m, 3H), 2.25-2.36 (m, 1H), 2.63 (t, 1H), 2.99 (d, J=16.4 Hz, 1H), 3.10 (dd, J=15.5, 5.7 Hz, 1H), 3.23-3.32 (m, 1H), 5.21-5.25 (m, 1H), 5.62-5.67 (m, 1H), 6.50 (s, 1H), 6.78 (s, 1H), 7.54-7.58 (m, 1H), 7.66-7.70 (m, 1H), 7.88 (s, 1H).

後処理

  1. additionis added
  2. customthe vessel sealed
  3. temperatureto cool
  4. extractionThe mixture is extracted with ethyl acetate
  5. washwashed with saturated aqueous sodium bicarbonate
  6. concentrationThe separated organic layer is concentrated in vacuo
  7. customis subjected to two sequential chromatography procedures (1: Silica gel, 1:50 to 1:25 methanol:methylene chloride. 2: Reverse phase HPLC, gradient 10-95% % Acetonitrile:Water, pH2, over 8 minutes)
  8. customto give the product

出典と根拠

ORDレコード
ord-ca1babbab27444ebb106233ae63c6c75
出典データセット
uspto-grants-2014_09
特許番号
US08835646B2

反応ノート

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