Potassium Carbonate → Cyp11B2-IN-1

HRID 1048951Notes

Reaction equation

HRID 1048951 reaction equation
[CH:1]1([NH:4][C:5]2[C:6]([NH2:12])=[CH:7][CH:8]=[C:9]([F:11])[CH:10]=2)[CH2:3][CH2:2]1.[OH:13][C:14]([C:17]1[CH:18]=[C:19]([CH:23]=O)[CH:20]=[N:21][CH:22]=1)([CH3:16])[CH3:15].OOS([O-])=O.[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.C(OCC)(=O)C>[CH:1]1([N:4]2[C:5]3[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=3[N:12]=[C:23]2[C:19]2[CH:18]=[C:17]([C:14]([OH:13])([CH3:15])[CH3:16])[CH:22]=[N:21][CH:20]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 23707502Potassium hydroxy sulfiteHCID 545925541-N-cyclopropyl-5-fluorobenzene-1,2-diamineHCID 867030855-(2-Hydroxypropan-2-yl)nicotinaldehyde

Product 1

HCID 56645363Cyp11B2-IN-1

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of N2-cyclopropyl-4-fluorobenzene-1,2-diamine (0.479 g, 2.88 mmol) in DMF (6.97 mL) and water (0.23 mL) were added the title compound from Step C (0.302 g, 1.83 mmol) and OXONE® (0.729 g, 1.19 mmol). The resulting mixture was stirred at room temperature for 1 hour, then diluted with ethyl acetate and water. Solid potassium carbonate was added until the aqueous layer was basic (pH ˜9). Ethyl acetate was added, and the organic layer was separated, washed with water and brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica gel (100% ethyl acetate) provided a product that was further purified by reverse phase HPLC(C18 OBD column, 20 to 90% acetonitrile/water, both 0.1% v/v trifluoroacetitic acid). Fractions containing the desired product were combined, washed sequentially with aqueous 1 N sodium hydroxide solution and brine, dried over magnesium sulfate, filtered and concentrated to provide the title compound: LCMS m/z 312.01 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.09 (d, J=1.7 Hz, 1 H), 9.85 (d, J=1.9 Hz, 1 H), 8.40 (s, 1 H), 7.73 (dd, J=8.8, 4.8 Hz, 1 H), 7.29 (dd, J=8.7, 2.2 Hz, 1 H), 7.08-7.04 (m, 1 H), 3.57-3.55 (m, 1 H), 2.21 (br s, 1 H), 1.69 (s, 6 H), 1.20-1.16 (m, 2 H), 0.79-0.75 (m, 2 H).

Workup

  1. customthe organic layer was separated
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography on silica gel (100% ethyl acetate)
  7. customprovided a product that
  8. customwas further purified by reverse phase HPLC(C18 OBD column, 20 to 90% acetonitrile/water
  9. additionFractions containing the desired product
  10. washwashed sequentially with aqueous 1 N sodium hydroxide solution and brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-d7cdeb23d0e44ce18751209c38848743
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

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