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

HRID 1877973노트

반응식

HRID 1877973 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
130 °C

실험 절차

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+H); 1H NMR (400 MHz, CDCl3) δ ppm 1.47-1.61 (m, 1 H), 1.85-1.99 (m, 1 H), 2.01-2.16 (m, 3 H), 2.25-2.36 (m, 1 H), 2.63 (t, 1 H), 2.99 (d, J=16.4 Hz, 1 H), 3.10 (dd, J=15.5, 5.7 Hz, 1 H), 3.23-3.32 (m, 1 H), 5.21-5.25 (m, 1 H), 5.62-5.67 (m, 1 H), 6.50 (s, 1 H), 6.78 (s, 1 H), 7.54-7.58 (m, 1 H), 7.66-7.70 (m, 1 H), 7.88 (s, 1 H).

후처리

  1. customthe vessel sealed
  2. temperatureto cool
  3. extractionThe mixture is extracted with ethyl acetate
  4. washwashed with saturated aqueous sodium bicarbonate
  5. concentrationThe separated organic layer is concentrated in vacuo
  6. 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)
  7. customto give the product

출처 및 근거

ORD 기록
ord-46d2880fb7ca4b838f8d9dccbb3127b6
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08314097B2

반응 노트

불러오는 중…