Sulfur → N-(cyclopropylmethyl)-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)nicotinamide

HRID 68928노트

반응식

HRID 68928 반응식
[CH:1]1([CH2:4][NH:5][C:6](=[O:30])[C:7]2[CH:12]=[C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[N:17]=[C:16]4[CH:28]=O)[CH:10]=[N:9][CH:8]=2)[CH2:3][CH2:2]1.[N:31]1[CH:36]=[C:35]([NH2:37])[C:34]([NH2:38])=[C:33]([C:39]2[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=2)[CH:32]=1.[S]>CN(C=O)C>[CH:1]1([CH2:4][NH:5][C:6](=[O:30])[C:7]2[CH:12]=[C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[N:17]=[C:16]4[C:28]3[NH:37][C:35]4[CH:36]=[N:31][CH:32]=[C:33]([C:39]5[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=5)[C:34]=4[N:38]=3)[CH:10]=[N:9][CH:8]=2)[CH2:2][CH2:3]1

참가 물질

5

반응물 3

HCID 5362487SulfurHCID 46315401[3,3'-Bipyridine]-4,5-diamineHCID 58138439N-(cyclopropylmethyl)-5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)nicotinamide

생성물 1

HCID 135987326N-(cyclopropylmethyl)-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)nicotinamide수율 23%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
4 °C

실험 절차

A solution of N-(cyclopropylmethyl)-5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)nicotinamide (XXXI) (0.404 g, 1.0 mmol), 3,3′-bipyridine-4,5-diamine (XV) (186 mg, 1.0 mmol) and sulfur (35 mg, 1.1 mmol) in dry DMF (10 mL) was heated at 140° C. overnight. The reaction was cooled and evaporated under vacuum. The residue was suspended in water, sonicated and filtered. The solid was washed with cold water and dried under vacuum. The crude product was dissolved in DCM and cooled to 4° C. overnight to get N-(cyclopropylmethyl)-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)nicotinamide (XXXII) as a brown solid (130 mg, 0.23 mmol, 23% yield). 1H NMR (DMSO-d6) δ ppm 0.19-0.37 (m, 2H), 0.36-0.58 (m, 2H), 0.97-1.115 (m, 1H), 1.67 (br, 2H), 2.14 (d, J=9.98 Hz, 2H), 2.40-2.46 (m, 1H), 3.20-3.33 (m, 3H), 3.75-4.14 (m, 2H), 6.13 (d, J=8.29 Hz, 1H), 7.60 (dd, J=7.82, 4.80 Hz, 1H), 7.92-8.12 (m, 3H), 8.20 (d, J=8.67 Hz, 1H), 8.55-8.67 (m, 2H), 8.94 (br s, 3H), 9.06 (d, J=1.88 Hz, 1H), 9.19 (d, J=1.87 Hz, 1H); ESIMS found C33H30N8O2 m/z 571 (M+H).

후처리

  1. temperatureThe reaction was cooled
  2. customevaporated under vacuum
  3. customsonicated
  4. filtrationfiltered
  5. washThe solid was washed with cold water
  6. customdried under vacuum
  7. dissolutionThe crude product was dissolved in DCM

출처 및 근거

ORD 기록
ord-7284ce091d0d4d73ab5485e60d960e4a
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822478B2

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