1,2-Dichloroethane → HCID 46215628、化合物

HRID 1472586ノート

反応式

HRID 1472586 の反応式
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:20]=2[C:21]([OH:23])=O)=[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]=[CH:26][C:25]([F:28])=[CH:24][C:20]=2[C:21]([NH:37][O:38][CH3:39])=[O:23])=[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 66769562HCID 66769562、化合物

生成物 1

HCID 46215628HCID 46215628、化合物収率 48.8%

試薬・触媒・溶媒 3

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

実験手順

To the solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluorobenzoic acid (1128 mg, 2.79 mmol) in N,N-dimethylformamide (DMF) (20 mL) was added HOBT (513 mg, 3.35 mmol) followed by EDC (643 mg, 3.35 mmol) and the reaction mixture stirred for 30 min. To this solution was added o-methoxylamine hydrochloride (280 mg, 3.35 mmol) and after 30 min, at 0° C. DIEA (1.460 mL, 8.38 mmol) was added. The reaction mixture was stirred at room temperature 24 hr. Water (100 mL) was added followed by acetic acid (1 mL) and the solution extracted with 2×50 ml of ethyl acetate. The organic layer was separated, washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and evaporated. The resulting oil was suspended in dichloromethane and filtered. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluoro-N-(methyloxy)benzamide (620 mg, 1.361 mmol, 48.7% yield) was isolated as a white solid. 1H NMR (400 MHz, DMSO-d6) ppm 1.26 (d, J=6.57 Hz, 6 H) 2.10 (s, 3 H) 3.69 (s, 3 H) 4.38 (quin, J=6.57 Hz, 1 H) 5.92 (s, 1 H) 6.50 (s, 1 H) 7.41-7.52 (m, 2 H) 7.58 (dd, J=8.72, 4.67 Hz, 1 H) 7.96 (s, 1 H) 8.46 (s, 1 H) 9.10 (s, 1 H) 11.95 (s, 1 H); HPLC Rt=2.24 min, MS (ESI): 433.4 [M+H]+.

後処理

  1. waitafter 30 min
  2. customat 0° C
  3. stirringThe reaction mixture was stirred at room temperature 24 hr
  4. extractionthe solution extracted with 2×50 ml of ethyl acetate
  5. customThe organic layer was separated
  6. washwashed with 2×50 ml
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. filtrationfiltered

出典と根拠

ORDレコード
ord-ce7d0eb8dc8c4015897d5855dd5bc591
出典データセット
uspto-grants-2015_04
特許番号
US09012479B2

反応ノート

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