Water → HCID 178422876, compound

HRID 1518153Notes

Reaction equation

HRID 1518153 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([NH2:16])=[C:11]([NH2:17])[CH:10]=1.[O:18]1[C:22]2([CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:21][C:20]([CH:28]=O)=[N:19]1.O>CN(C=O)C>[CH3:15][C:13]1[C:12]2[NH:16][C:28]([C:20]3[CH2:21][C:22]4([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]4)[O:18][N:19]=3)=[N:17][C:11]=2[CH:10]=[C:9]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])[CH:14]=1

Participants

5

Reactant 3

HCID 962WaterHCID 592800862',6'-Difluoro-5-methyl-biphenyl-3,4-diamineHCID 592801071-Oxa-2-aza-spiro[4.5]dec-2-ene-3-carbaldehyde

Product 1

HCID 178422876HCID 178422876, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

2′,6′-Difluoro-5-methyl-biphenyl-3,4-diamine (186 mg, 0.792 mmol, as prepared in the previous step) was placed in an 8 mL vial equipped with a stir bar, and dry DMF (2 mL) was added. 1-Oxa-2-aza-spiro[4.5]dec-2-ene-3-carbaldehyde (122 mg, 0.730 mmol, as prepared in step B of this Example) was added as a solution in DMF (2 mL). Solid Na2S2O5 (153 mg, 0.803 mmol) was added, and the mixture was heated to 100° C. for 4 h. The cooled mixture was poured into water (100 mL) and extracted three times with EtOAc (50 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. The residue was purified by column chromatography using a 4-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 3:17, v/v over 30 min, yielding 105 mg (38%) of the title compound. 1H-NMR (400 MHz, d6-DMSO) δ: 7.43-7.55 (m, 2H), 7.15-7.30 (m, 3H), 3.35 (s, 2H), 2.61 (s, 3H), 1.63-1.83 (m, 6H), 1.34-1.57 (m, 4H). Mass Spectrum (LCMS, ESI pos.): Calcd. for C22H21F2N3O: 382.2 (M+H). found: 382.2.

Workup

  1. customvial equipped with a stir bar
  2. extractionextracted three times with EtOAc (50 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. customthe solvents were removed under reduced pressure
  6. customThe residue was purified by column chromatography
  7. washeluting with EtOAc/hexanes, 0:1 to 3:17, v/v over 30 min

Sources & evidence

ORD record
ord-d89c10722bd74f7c859e98ec81604fd8
Source dataset
uspto-grants-2012_07
Patent number
US08232409B2

Reaction notes

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