Phosphorus tribromide → HCID 58528998, compound

HRID 1431014Notes

Reaction equation

HRID 1431014 reaction equation
O[CH2:2][C:3]1[N:4]=[CH:5][C:6]([NH:9][C:10](=[O:32])[C:11]2[CH:16]=[C:15]([O:17][C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH:14]=[C:13]([O:28][CH:29]([CH3:31])[CH3:30])[CH:12]=2)=[N:7][CH:8]=1.P(Br)(Br)Br.[CH2:37]([O:39][P:40]([O:44]CC)[O:41][CH2:42][CH3:43])[CH3:38]>ClC(Cl)C.C(Cl)Cl>[CH:29]([O:28][C:13]1[CH:12]=[C:11]([CH:16]=[C:15]([O:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:20][CH:19]=2)[CH:14]=1)[C:10]([NH:9][C:6]1[CH:5]=[N:4][C:3]([CH2:2][P:40](=[O:44])([O:41][CH2:42][CH3:43])[O:39][CH2:37][CH3:38])=[CH:8][N:7]=1)=[O:32])([CH3:30])[CH3:31]

Participants

6

Reactant 3

HCID 24614Phosphorus tribromideHCID 31215Triethyl phosphiteHCID 58528856HCID 58528856, compound

Product 1

HCID 58528998HCID 58528998, compoundYield 20.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of N-(5-hydroxymethyl-pyrazin-2-yl)-3-isopropoxy-5-(4-methanesulfonyl-phenoxy)-benzamide (130 mg, 0.28 mmol) in 2.8 mL of dichloroethane was added 0.56 mL of a 1 M solution of PBr3 in CH2Cl2 and the solution stirred for 4 h at rt. Then triethylphosphite (0.5 mL, 2.8 mmol) was added and the resulting solution microwave heated at 120° C. for 5 min. Then the mixture was diluted with CH2Cl2 and washed with aqueous NaHCO3, 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): 65-95 (30 min ramp) to provide 33 mg (20%) of the title compound. 1H NMR (500 MHz, DMSO-d6): δ 1.19 (t, 6H, J=6 Hz), 1.30 (d, 6H, J=6 Hz), 3.22 (s, 3H), 3.50 (d, 2H, J=21 Hz), 4.02 (m, 4H), 4.78 (septet, 1H, J=6 Hz), 6.97 (t, 1H, J=2 Hz), 7.25 (d, 2H, J=8 Hz), 7.35 (t, 1H, J=2 Hz), 7.51 (t, 1H, J=2 Hz), 7.95 (d, 2H, J=8 Hz), 8.41 (dd, 1H, J=1, 2 Hz), 9.29 (d, 11-1, =1 Hz). 11.17 (s, 1H); LCMS (m/z): 578.6 [C26H32N3O3PS+H]+.

Workup

  1. temperaturethe resulting solution microwave heated at 120° C. for 5 min
  2. washwashed with aqueous NaHCO3, brine
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. washeluting with % EtOAc in hexanes (time)

Sources & evidence

ORD record
ord-2cdfcbaf3a5045779110b16216b0e230
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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