1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 5-chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluoro-N-(N-methylsulfamoyl)benzamide

HRID 1849531ノート

反応式

HRID 1849531 の反応式
[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:23]=[C:22]3[C:17]([CH2:18][CH2:19][C:20]([CH3:25])([CH3:24])[O:21]3)=[CH:16][CH:15]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].[CH3:26][NH:27][S:28](=[O:31])(=[O:30])[NH2:29].Cl.C(N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl.Cl>[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:23]=[C:22]3[C:17]([CH2:18][CH2:19][C:20]([CH3:25])([CH3:24])[O:21]3)=[CH:16][CH:15]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:29][S:28](=[O:31])(=[O:30])[NH:27][CH3:26])=[O:8]

参加物

7

反応物 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 13168287(Methylsulfamoyl)amineHCID 867028665-Chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluorobenzoic acid

生成物 1

HCID 867028755-chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluoro-N-(N-methylsulfamoyl)benzamide収率 56%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 313Hydrochloric Acid溶媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of 5-chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluorobenzoic acid (50 mg, 0.14 mmol), methyl(sulfamoyl)amine (23 mg, 0.21 mmol), 1-ethyl-(3-dimethylamino-propyl)carbodiimide hydrochloride (40 mg, 0.21 mmol) and 4-dimethylaminopyridine (26 mg, 0.21 mmol) in DCM (20 mL) was stirred at room temperature for 16 hrs. The mixture was diluted with HCl (2.0 N, 20 mL) and extracted with EtOAc (50×3 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by reverse phase Combiflash (18%-25% MeCN in 0.5% NH4HCO3) to give target product (35.4 mg, 56%) as a pale yellow solid. LCMS (ESI) Method A: RT=5.78 min, m/z: 456.7 [M+H]+; 1H-NMR (500 MHz, MeOH-d4,): δ 7.77 (d, J=6.0 Hz, 1H), 7.42 (d, J=10.5 Hz, 1H), 6.99 (d, J=8.5 Hz, 1H), 6.52 (dd, J=9.0, 2.5 Hz, 1H), 6.36 (d, J=2.5 Hz, 1H), 5.14 (s, 2H), 2.74 (t, J=6.5 Hz, 2H), 2.71 (s, 3H), 1.80 (t, J=6.5 Hz, 2H), 1.32 (s, 6H).

後処理

  1. extractionextracted with EtOAc (50×3 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by reverse phase Combiflash (18%-25% MeCN in 0.5% NH4HCO3)

出典と根拠

ORDレコード
ord-42256e8677bb4a1dbf8cd989cf23e9a5
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

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