1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 44603145, compound

HRID 79062Notes

Reaction equation

HRID 79062 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)=[C:4]([F:21])[CH:3]=1.Cl.[NH2:23][O:24][CH2:25][C@@H:26]([OH:28])[CH3:27].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[OH:28][C@@H:26]([CH3:27])[CH2:25][O:24][NH:23][C:18]([C:17]1[C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=2[F:21])=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][N:12]=[CH:11]2)=[O:20]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 670840974-(4-bromo-2-fluorophenylamino)-1H-indazole-5-carboxylic acidHCID 86637725(S)-1-aminooxypropan-2-ol hydrochloride

Product 1

HCID 44603145HCID 44603145, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(4-bromo-2-fluorophenylamino)-1H-indazole-5-carboxylic acid (115 mg, 0.33 mmol) and (S)-1-aminooxy-propan-2-ol hydrochloride (63 mg, 0.49 mmol) in DMF (3 mL) was added EDCI (69 mg, 0.36 mmol), HOBt (49 mg, 0.36 mmol) and DIPEA (150 μL, 0.85 mmol). The reaction mixture was stirred at room temperature for 16 hours before being concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (10 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to reverse phase preparative HPLC (10-90% acetonitrile/water 0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm). The resultant product was dissolved in ethyl acetate (5 mL) and washed with aqueous saturated sodium bicarbonate solution (10 mL). The aqueous fraction was extracted twice with ethyl acetate (2×10 mL) and the combined organic layers washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo to yield the title compound as a white solid (61 mg, 44%). LCMS (Method A): RT=8.45 min, [M+H]+=423/425. 1H NMR (DMSO-d6, 400 MHz) 13.21 (1H, s), 11.63 (1H, s), 9.90 (1H, s), 7.58 (1H, dd, J=10.47, 2.24 Hz), 7.46 (1H, d, J=8.75 Hz), 7.29 (1H, ddd, J=8.59, 2.19, 1.06 Hz), 7.23 (1H, s), 7.08 (1H, t, J=8.80 Hz), 7.02 (1H, d, J=8.78 Hz), 4.77 (1H, d, J=4.15 Hz), 3.84-3.78 (1H, m), 3.70-3.61 (2H, m), 1.03 (3H, d, J=6.33 Hz).

Workup

  1. concentrationbefore being concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in ethyl acetate (10 mL)
  3. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  4. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
  5. washThe combined organic fractions were washed with brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resultant product was dissolved in ethyl acetate (5 mL)
  9. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  10. extractionThe aqueous fraction was extracted twice with ethyl acetate (2×10 mL)
  11. washthe combined organic layers washed with brine (20 mL)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e1ced0a3c8814e89affbe99648b7e825
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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