Triethylamine → HCID 11511107, compound

HRID 494690Notes

Reaction equation

HRID 494690 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]([C:19](O)=[O:20])=[CH:17][C:12]3[C:13]([CH3:16])=[N:14][O:15][C:11]=3[C:10]=2[F:22])=[C:4]([Cl:23])[CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.[CH:41]1([CH2:44][O:45][NH2:46])[CH2:43][CH2:42]1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.CCOC(C)=O>[CH:41]1([CH2:44][O:45][NH:46][C:19]([C:18]2[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[Cl:23])=[C:10]([F:22])[C:11]3[O:15][N:14]=[C:13]([CH3:16])[C:12]=3[CH:17]=2)=[O:20])[CH2:43][CH2:42]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11182605O-(cyclopropylmethyl)hydroxylamineHCID 11567514HCID 11567514, compound

Product 1

HCID 11511107HCID 11511107, compoundYield 47.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methylbenzo[d]isoxazole-5-carboxylic acid (9a) (50.0 mg, 0.125 mmol) in DMF (1 mL) was added HOBt (24.6 mg, 0.161 mmol), Et3N (0.060 mL, 0.43 mmol), O-cyclopropylmethyl-hydroxylamine (15.5 mg, 0.178 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (32.2 mg, 0.168 mmol) at room temperature. After 6 days, the reaction mixture was diluted with EtOAc, washed with saturated aqueous NH4Cl, brine, saturated aqueous NaHCO3, and brine. The organic layer was dried over MgSO4, filtered, concentrated in vacuo, and purified by flash column chromatography using the Biotage system (0.5% MeOH in CH2Cl2) to give 27.6 mg (47% yield) of the desired product (10a). MS APCI (−) m/z 466, 468 (M+, Br, Cl pattern) detected. 1H NMR (400 MHz, CD3OD) δ 7.82 (s, 1H), 7.57 (d, 1H), 7.31 (dd, 1H), 6.74 (dd, 1H), 3.73 (d, 2H), 2.60 (s, 3H), 1.16 (m, 1H), 0.55 (m, 2H), 0.28 (m, 2H). 19F NMR (376 MHz, CD3OD)−140.96 (s, 1F).

Workup

  1. washwashed with saturated aqueous NH4Cl, brine, saturated aqueous NaHCO3, and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-5961f284b43b4131bc509e7024bd5063
Source dataset
uspto-grants-2009_05
Patent number
US07538120B2

Reaction notes

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