Triethylamine → HCID 58528851, compound

HRID 1431012Notes

Reaction equation

HRID 1431012 reaction equation
[NH2:1][C:2]1[CH:17]=[C:16]([F:18])[C:15]([S:19][C:20]2[N:21]([CH3:25])[CH:22]=[CH:23][N:24]=2)=[CH:14][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][N:8]=1)=[O:5].[CH3:26][PH:27](=[O:32])[O:28][CH:29]([CH3:31])[CH3:30].C(N(CC)CC)C.C([SiH](CC)CC)C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(C)C=CC=CC=1>[CH:29]([O:28][P:27]([C:10]1[CH:9]=[N:8][C:7]([NH:6][C:4](=[O:5])[C:3]2[CH:14]=[C:15]([S:19][C:20]3[N:21]([CH3:25])[CH:22]=[CH:23][N:24]=3)[C:16]([F:18])=[CH:17][C:2]=2[NH2:1])=[CH:12][CH:11]=1)([CH3:26])=[O:32])([CH3:31])[CH3:30]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 12052TriethylsilaneHCID 58528795HCID 58528795, compoundHCID 178460552HCID 178460552, compound

Product 1

HCID 58528851HCID 58528851, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-amino-N-(5-bromo-pyridin-2-yl)-4-fluoro-5-(1-methyl-1H-imidazol-2-ylsulfanyl)-benzamide (346 mg, 0.82 mmol), isopropyl methylphosphinate (0.256 mL, 2.05 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride (60 mg, 0.082 mmol) and 8 mL of toluene was degassed by bubbling N2 through it for 2 min, then triethylamine (0.285 mL, 2.05 mmol) and triethylsilane (0.033 mL, 0.205 mmol) were added and the mixture microwave heated at 150° C. for 10 min. The solvent was evaporated and the residue dissolved in CH2Cl2, washed with brine, dried (MgSO4) and evaporated. The residue was adsorbed to SiO2 and subjected to MPLC on a 12 g SiO2 column eluting with % EtOAc in hexanes (time): 75 (8 min), 85 (10 min), 90 (10 min), 100 (20 min), then % MeOH in EtOAc (time): 1 (10 min), 2 (10 min) to provide 60 mg (16%) of the title compound. 1H NMR (500 MHz, DMSO-do): δ 1.11 (d, 3H, J=6 Hz), 1.29 (d, 3H, J=6 Hz), 1.69 (d, 3H, J=15 Hz), 3.68 (s, 3H), 4.40 (septet, 1H, J=6 Hz), 6.60 (d, 1H, J=12 Hz), 6.90 (d, 1H, J=1 Hz), 6.98 (s, 2H), 7.27 (d, 1H, J=1 Hz), 8.02 (d, 1H, J=8 Hz), 8.12 (td, 1H, J=7, 3 Hz), 8.17 (dd, 1H, J=7, 2 Hz), 8.67 (dt, 1H, J=5, 1 Hz), 11.02 (s, 1H); LCMS (m/z): 464.1 [C20H23FN5O3PS+H]+.

Workup

  1. customwas degassed
  2. customby bubbling N2 through it for 2 min
  3. customThe solvent was evaporated
  4. dissolutionthe residue dissolved in CH2Cl2
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. washeluting with % EtOAc in hexanes (time)

Sources & evidence

ORD record
ord-72f79a0d3cdd481c97814306396daa4d
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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