Triethylamine → 6-{[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carbonyl]-amino}-5-cyano-1H-indazole-7-carboxylic acid bicyclopropyl-1-ylamide

HRID 245613노트

반응식

HRID 245613 반응식
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]3[O:22][C:21](=[O:23])[C:20]4[C:15](=[C:16]([C:27]#[N:28])[CH:17]=[C:18]5[CH:26]=[N:25][NH:24][C:19]5=4)[N:14]=3)=[CH:11][C:10]([C:29]([F:32])([F:31])[F:30])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl.[C:34]1([NH2:40])([CH:37]2[CH2:39][CH2:38]2)[CH2:36][CH2:35]1.C(N(CC)CC)C>CN(C)C=O>[C:34]1([NH:40][C:21]([C:20]2[C:15]([NH:14][C:13]([C:12]3[N:8]([C:3]4[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=4)[N:9]=[C:10]([C:29]([F:31])([F:30])[F:32])[CH:11]=3)=[O:22])=[C:16]([C:27]#[N:28])[CH:17]=[C:18]3[C:19]=2[NH:24][N:25]=[CH:26]3)=[O:23])([CH:37]2[CH2:39][CH2:38]2)[CH2:36][CH2:35]1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 53433499(1,1'-Bi(cyclopropan))-1-amine hydrochlorideHCID 579901177-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-9-oxo-1,9-dihydro-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalene-5-carbonitrile

생성물 1

HCID 579901396-{[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carbonyl]-amino}-5-cyano-1H-indazole-7-carboxylic acid bicyclopropyl-1-ylamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

To a solution of 500 mg of the above 7-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-9-oxo-1,9-dihydro-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalene-5-carbonitrile in 8 mL of N,N-dimethylformamide is added 218 mg (1.63 mmol) of bicyclopropyl-1-ylamine hydrochloride and 303 μL (2.18 mmol) of triethylamine. The reaction is stirred at 60° C. for 24 hours and then concentrated in vacuo. The residue is taken-up with water and ethyl acetate. The phases are separated and the aqueous layer is washed with ethyl acetate. The combined organic layers are washed several times with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography (SiO2, hexanes/ethyl acetate 3:9) affords 76 mg (12% over two steps) of the product as white solid; LC/MS: 555/557 (M+H)+.

후처리

  1. concentrationconcentrated in vacuo
  2. customThe phases are separated
  3. washthe aqueous layer is washed with ethyl acetate
  4. washThe combined organic layers are washed several times with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash chromatography (SiO2, hexanes/ethyl acetate 3:9)

출처 및 근거

ORD 기록
ord-b4e370db32ee404585341ad93aa80851
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658801B2

반응 노트

불러오는 중…