1,2-Dichloroethane → HCID 46215627, 화합물

HRID 62532노트

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HRID 62532 반응식
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([NH:11][C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[C:22]([CH3:28])[CH:21]=3)[CH:13]=2)[CH:3]=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[CH:10]=[CH:9][C:5]([C:6]([NH:37][O:38][CH3:39])=[O:8])=[C:4]([NH:11][C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[C:22]([CH3:28])[CH:21]=3)[CH:13]=2)[CH:3]=1

참가 물질

8

반응물 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 667692534-Chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]benzoic acid

생성물 1

HCID 46215627HCID 46215627, 화합물수율 29.1%

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

To the solution of 4-chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]benzoic acid (260 mg, 0.619 mmol) in N,N-dimethylformamide (DMF) (20 mL) was added HOBT (114 mg, 0.742 mmol) and EDC (142 mg, 0.742 mmol) and the reaction mixture was stirred for 30 min. To this solution was added O-methoxylamine hydrochloride (62.0 mg, 0.742 mmol), and after 30 min the reaction was cooled to 0° C. and DIEA (0.323 mL, 1.856 mmol) was added. The reaction mixture was stirred at the room temperature over the weekend. Water (100 mL) followed by acetic acid (1 mL) were added and the reaction mixture was extracted with 2×50 ml of ethyl acetate. The organic layer was washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and evaporated. The resulting yellow oil was purified by flash column chromatography on silica gel using DCM:EtOAc (10% to 100%). 4-Chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide (85 mg, 0.180 mmol, 29.1% yield) was isolated as white foam. 1H NMR (400 MHz, DMSO-d6) ppm 1.27 (d, J=6.57 Hz, 6 H) 2.12 (s, 3 H) 3.70 (s, 3 H) 4.41 (quin, J=6.57 Hz, 1 H) 5.95 (s, 1 H) 6.66 (s, 1 H) 7.01-7.39 (m, 1 H) 7.55-7.88 (m, 2 H) 8.02 (s, 1 H) 8.60 (s, 1 H) 9.76 (br. s., 1 H) 12.01 (br. s., 1 H); HPLC Rt=2.50 min, MS (ESI): 449.0, 451.1 [M+H]+.

후처리

  1. stirringThe reaction mixture was stirred at the room temperature over the weekend
  2. additionwere added
  3. extractionthe reaction mixture was extracted with 2×50 ml of ethyl acetate
  4. washThe organic layer was washed with 2×50 ml
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe resulting yellow oil was purified by flash column chromatography on silica gel

출처 및 근거

ORD 기록
ord-ba8ab3333608462994237cbc2d6c127d
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09446034B2

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