Triphenylphosphine → HCID 136640165, compound

HRID 1748814Notes

Reaction equation

HRID 1748814 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[S:14][CH2:13][C@H:12]([CH2:15]O)[NH:11][C:10]3[N:17]([CH3:26])[N:18]=[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[C:9]2=3)=[C:4]([CH3:27])[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[N:48]1C(=O)CC[C:49]1=O.C([Na])#N>C(Cl)Cl.CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[S:14][CH2:13][C@H:12]([CH2:15][C:49]#[N:48])[NH:11][C:10]3[N:17]([CH3:26])[N:18]=[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[C:9]2=3)=[C:4]([CH3:27])[CH:3]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 136639983HCID 136639983, compoundHCID 178511850HCID 178511850, compound

Product 1

HCID 136640165HCID 136640165, compoundYield 3.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of rac-((4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-yl)methanol (0.070 g, 0.16 mmol, Example #K.10) and triphenylphosphine (0.041 g, 0.16 mmol) in DCM (5 ml)/DMF (0.5 ml) at 0° C. was added 1-bromopyrrolidine-2,5-dione (0.028 g, 0.16 mmol). The reaction was stirred at 0° C. for about 2 h. The reaction was partitioned between DCM (25 mL) and saturated solution of NaHCO3 (40 mL). The organic layer was dried with Na2SO4, filtered and was concentrated in vacuo. The resulting residue was dissolved in DMF (1.5 ml) and cyanosodium (0.077 g, 1.57 mmol) was added. The reaction was heated at about 100° C. for about 1 h. The reaction was partitioned between EtOAc (25 mL) and brine (25 mL). The organic layer was washed with brine (25 mL), dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, 0-50% EtOAc/heptane) to give rac-2-((4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-yl)acetonitrile (0.005 g, 0.005 mmol, 3%) as a white solid: LC-MS (Table 1, Method g): LC-MS (Table 1, Method g) Rt=2.57 min, m/z 454/456 (M+H)+; 1H-NMR (DMSO-d6, Bruker 400 MHz) δ 8.48-8.45 (m, 1H), 7.83-7.80 (m, 1H), 7.75-7.70 (m, 1H), 7.36 (d, J=2.0 Hz, 1H), 7.26-7.17 (m, 2H), 7.09 (d, J=8.3 Hz, 1H), 6.74 (s, 1H), 6.19 (d, J=5.7 Hz, 1H), 4.03-3.92 (m, 1H), 3.77 (s, 3H), 2.95-2.85 (m, 2H), 2.79-2.74 (m, 1H), 2.71-2.63 (m, 1H), 2.50 (s, 3H).

Workup

  1. customat 0° C.
  2. customThe reaction was partitioned between DCM (25 mL) and saturated solution of NaHCO3 (40 mL)
  3. dry with materialThe organic layer was dried with Na2SO4
  4. filtrationfiltered
  5. concentrationwas concentrated in vacuo
  6. dissolutionThe resulting residue was dissolved in DMF (1.5 ml)
  7. temperatureThe reaction was heated at about 100° C. for about 1 h
  8. customThe reaction was partitioned between EtOAc (25 mL) and brine (25 mL)
  9. washThe organic layer was washed with brine (25 mL)
  10. dry with materialdried with Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by column chromatography (SiO2, 0-50% EtOAc/heptane)

Sources & evidence

ORD record
ord-765538d171d1449aabd7a8842052261d
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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