1,2-Dichloroethane → HCID 46215630、化合物

HRID 62545ノート

反応式

HRID 62545 の反応式
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:20]=2[C:21](O)=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1.C1C=CC2[N:37]([OH:38])N=NC=2C=1.[CH2:39](Cl)CCl.CCN(C(C)C)C(C)C>CN(C)C=O.C(O)(=O)C.O>[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:20]=2[C:21]([NH:37][O:38][CH3:39])=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:15])[CH3:16])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1

参加物

8

反応物 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 667696182-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-4-fluorobenzoic acid

生成物 1

HCID 46215630HCID 46215630、化合物収率 35.5%

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-4-fluorobenzoic acid (2.5 g, 6.19 mmol) in N,N-dimethylformamide (DMF) (50 mL) was added HOBT (1.138 g, 7.43 mmol) and EDC (1.424 g, 7.43 mmol) and the reaction mixture was stirred for 30 min. To this solution was added O-methoxylamine hydrochloride (0.620 g, 7.43 mmol) and after 30 min the mixture was cooled to 0° C. Then DIEA (3.23 mL, 18.57 mmol) was added. The reaction mixture was stirred at the room temperature for 24 hr. Water (100 mL) followed by acetic acid (1 mL) were added and the solution extracted with 2×50 ml of ethyl acetate. The organic layer was washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and condensed. The resulting oil was purified by flash column chromatography on silica gel (2:1 DCM: EtOAc). 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-4-fluoro-N-(methyloxy)benzamide (1 g, 2.195 mmol, 35.5% yield) was isolated as a yellow foam. 1H NMR (400 MHz, DMSO-d6) ppm 1.28 (d, J=6.57 Hz, 6 H) 2.11 (s, 3 H) 3.71 (s, 3 H) 4.41 (quin, J=6.51 Hz, 1 H) 5.97 (s, 1 H) 6.74 (s, 1 H) 6.87-7.06 (m, 1 H) 7.39 (dd, J=11.37, 2.53 Hz, 1 H) 7.66 (dd, J=8.46, 6.69 Hz, 1 H) 8.03 (s, 1 H) 8.57 (s, 1 H) 9.96 (br. s., 1 H) 11.98 (br. s., 1 H); HPLC Rt=2.36 min, MS (ESI): 433.3 [M+H]+.

後処理

  1. stirringThe reaction mixture was stirred at the room temperature for 24 hr
  2. additionwere added
  3. extractionthe solution extracted with 2×50 ml of ethyl acetate
  4. washThe organic layer was washed with 2×50 ml
  5. dry with materialdried over MgSO4 and condensed
  6. customThe resulting oil was purified by flash column chromatography on silica gel (2:1 DCM: EtOAc)

出典と根拠

ORDレコード
ord-c5db5b44a408477ab7f40be9a80adc78
出典データセット
uspto-grants-2016_09
特許番号
US09446034B2

反応ノート

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