Water → HCID 136348434, compound

HRID 1748766Notes

Reaction equation

HRID 1748766 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:25])=[C:6]([CH:8]2[S:14][CH2:13][CH2:12][NH:11][C:10]3[N:15]([CH3:24])[N:16]=[C:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=4)[C:9]2=3)[CH:7]=1.C(OCC)(=O)C.O.[CH3:33][N:34](C=O)C>[C-]#N.[Zn+2].[C-]#N.[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>[CH3:25][C:5]1[CH:4]=[CH:3][C:2]([C:33]#[N:34])=[CH:7][C:6]=1[CH:8]1[S:14][CH2:13][CH2:12][NH:11][C:10]2[N:15]([CH3:24])[N:16]=[C:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:9]1=2

Participants

7

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 136216127HCID 136216127, compound

Product 1

HCID 136348434HCID 136348434, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

To a degassed solution of 4-(5-bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.250 g, 0.6 mmol, Example D.27) in anhydrous DMF (3 mL) was added zinc cyanide (0.0511 g, 0.43 mmol) and tetrakis(triphenylphosphine)-palladium(0) (0.0346 g, 0.03 mmol). The resulting mixture was heated, in a sealed microwave vessel, for about 1 h, at about 120° C. in a microwave. After cooling to rt, ethyl acetate (50 mL) and water (50 mL) were added, and the mixture was filtered through a pad of Celite®. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, hexanes/ethyl acetate 1:1) followed by trituration with diethyl ether to give 4-methyl-3-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzonitrile (0.042 g, 0.117 mmol, 20%). LC-MS (Table 1, Method e) Rt=8.10 min, m/z 362 (M+H)+; 1H-NMR (DMSO-d6, Bruker 400 MHz) δ 2.57-2.66 (1 H, m) 2.63 (3 H, s) 2.70 (1 H, dd, J=14.7, 4.4 Hz) 3.04 (1 H, ddt, J=13.1, 10.6, 1.6 Hz) 3.68-3.77 (1 H, m) 3.79 (3 H, s) 5.87 (1 H, d, J=5.5 Hz) 6.87 (1 H, s) 7.17 (1 H, ddd, J=7.4, 4.9, 1.3 Hz) 7.34 (1 H, d, J=8.0 Hz) 7.46 (1 H, dd, J=7.8, 1.8 Hz) 7.54 (1 H, d, J=1.8 Hz) 7.70 (1 H, ddd, J=9.4, 7.3, 1.8 Hz) 7.86 (1 H, dt, J=8.0, 1.0 Hz) 8.46 (1 H, ddd, J=4.9, 1.9, 0.9 Hz).

Workup

  1. temperatureAfter cooling to rt
  2. filtrationthe mixture was filtered through a pad of Celite®
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (SiO2, hexanes/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-ebe12247d02a4783be89affdf2ad4f0d
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

Loading…