Diisopropylethylamine → HCID 52916969, compound

HRID 2172975Notes

Reaction equation

HRID 2172975 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[N:14][CH:15]=[C:16]([C:17]([NH:19][C:20]4([C:23]5[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=5)[C:26]([OH:28])=O)[CH2:22][CH2:21]4)=[O:18])[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[NH2:32][CH2:33][C:34]([O:36][CH3:37])=[O:35].Cl.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[CH3:37][O:36][C:34](=[O:35])[CH2:33][NH:32][C:26](=[O:28])[C:25]1[CH:29]=[CH:30][CH:31]=[C:23]([C:20]2([NH:19][C:17]([C:16]3[C:11]4[CH:10]=[N:9][N:8]([C:5]5[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=5)[C:12]=4[CH:13]=[N:14][CH:15]=3)=[O:18])[CH2:22][CH2:21]2)[CH:24]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 52916889HCID 52916889, compound

Product 1

HCID 52916969HCID 52916969, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(1-{[1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]-amino}-cyclopropyl)-benzoic acid (0.200 g, 0.480 mmol), Gly-OMe.HCl (68.1 mg, 0.543 mmol) and N,N-diisopropylethylamine (426 μL, 2.40 mmol) in DMF (4.5 mL) is added TBTU (192 mg, 0.600 mmol). After 4 hours, the mixture is concentrated in vacuo. The residue is dissolved in ethyl acetate (100 mL) and washed with 2N sodium hydroxide (3×50 mL), saturated aqueous ammonium chloride (2×50 mL), saturated aqueous sodium bicarbonate (50 mL), brine (50 mL). The organic layer is dried over MgSO4, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a gradient of 0-8% methanol in methylene chloride to give a foam, which is triturated with ether (3 mL), filtered, washed with cold ether (3×3 mL) and air dried to afford the title compound.

Workup

  1. concentrationthe mixture is concentrated in vacuo
  2. dissolutionThe residue is dissolved in ethyl acetate (100 mL)
  3. washwashed with 2N sodium hydroxide (3×50 mL), saturated aqueous ammonium chloride (2×50 mL), saturated aqueous sodium bicarbonate (50 mL), brine (50 mL)
  4. dry with materialThe organic layer is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel chromatography
  8. washeluting with a gradient of 0-8% methanol in methylene chloride
  9. customto give a foam, which
  10. customis triturated with ether (3 mL)
  11. filtrationfiltered
  12. washwashed with cold ether (3×3 mL) and air
  13. customdried

Sources & evidence

ORD record
ord-feba15eb86cf48b182e99955fb32536b
Source dataset
uspto-grants-2015_06
Patent number
US09056858B2

Reaction notes

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