Triphenylphosphine → HCID 66606084, compound

HRID 1811068Notes

Reaction equation

HRID 1811068 reaction equation
[Br:1][C:2]1[C:3]([CH3:19])=[C:4]([N:8]2[C:16](=[O:17])[C:15]3[CH:14]=[CH:13][N:12]=[CH:11][C:10]=3[C:9]2=O)[CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+].BrC1C(C)=C(NC(=O)C2C(CO)=CC=NC=2)C=CC=1.BrC1C(C)=C(NC(=O)C2C=CN=CC=2CO)C=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>CO>[Br:1][C:2]1[C:3]([CH3:19])=[C:4]([N:8]2[C:16](=[O:17])[C:15]3[CH:14]=[CH:13][N:12]=[CH:11][C:10]=3[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 4311764Sodium borohydrideHCID 66605655HCID 66605655, compoundHCID 66606433HCID 66606433, compoundHCID 66606575HCID 66606575, compound

Product 1

HCID 66606084HCID 66606084, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of 2-(3-bromo-2-methylphenyl)-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione (4.7 g, 14.82 mmol) in methanol (200 mL) was treated with sodium borohydride (2 g, 52.9 mmol) and stirred at rt for 1 h. The mixture was concentrated and the residue was treated with NaHCO3 (aq). The mixture was extracted several times with a mixture of DCM and methanol. The combined organic phases were washed with water, dried and concentrated to give a mixture of N-(3-bromo-2-methylphenyl)-4-(hydroxymethyl)-nicotinamide and N-(3-bromo-2-methylphenyl)-3-(hydroxymethyl)isonicotinamide as an off-white solid. Mass spectrum m/z 321, 323 (M+H)+. Without purification, this material was suspended in THF (250 mL) and treated with triphenylphosphine (polymer supported, 3 mmol P/g resin, 18.44 g, 54.8 mmol) and diethyl azodicarboxylate (6.45 g, 37.1 mmol) and the mixture was stirred at rt for 4 h. The mixture was filtered and concentrated, and the residue was dissolved in DCM, washed with water, NaHCO3 (aq) and brine, and dried and concentrated. The residue was subjected to column chromatography (eluting with EtOAc) to provide 2-(3-bromo-2-methylphenyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one as a white solid (Intermediate 44-1, 2.7 g, 60%). 1H NMR (400 MHz, chloroform-d) δ 9.21 (1H, d, J=0.88 Hz), 8.84 (1H, d, J=5.06 Hz), 7.63 (1H, dd, J=7.70, 1.32 Hz), 7.51 (1H, dd, J=5.06, 0.88 Hz), 7.22 (1H, dt, J=7.70, 1.32 Hz), 7.17 (1H, d, J=7.92 Hz), 4.76 (2H, s), 2.31 (3H, s). Mass spectrum m/z 303, 305 (M+H)+. Also obtained was (Z)-3-bromo-N-(furo[3,4-c]pyridin-1(3H)-ylidene)-2-methylaniline as a white solid (Intermediate 44-2, 760 mg, 17%), which also contained the isomeric (Z)-3-bromo-N-(furo[3,4-c]pyridin-3(1H)-ylidene)-2-methylaniline. 1H NMR (400 MHz, chloroform-d) δ 9.26 (1H, s), 8.80 (1H, d, J=5.06 Hz), 7.42 (1H, dd, J=5.06, 0.88 Hz), 7.31-7.35 (1H, m), 7.02-7.08 (2H, m), 5.39 (2H, s), 2.35 (3H, s). Mass spectrum m/z 303, 305 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. additionthe residue was treated with NaHCO3 (aq)
  3. extractionThe mixture was extracted several times
  4. additionwith a mixture of DCM and methanol
  5. washThe combined organic phases were washed with water
  6. customdried
  7. concentrationconcentrated
  8. customto give
  9. customWithout purification
  10. stirringthe mixture was stirred at rt for 4 h
  11. filtrationThe mixture was filtered
  12. concentrationconcentrated
  13. dissolutionthe residue was dissolved in DCM
  14. washwashed with water, NaHCO3 (aq) and brine
  15. customdried
  16. concentrationconcentrated
  17. washThe residue was subjected to column chromatography (eluting with EtOAc)

Sources & evidence

ORD record
ord-e33cb64df0464b3ba9d64000bf305199
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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