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 889136노트

반응식

HRID 889136 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

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 4oC 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
  8. temperaturecooled to 4oC overnight

출처 및 근거

ORD 기록
ord-e8e8dcbf89ab4007bd2f27abf745195d
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08252812B2

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