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 68928Notes

Reaction equation

HRID 68928 reaction equation
[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

Participants

5

Reactant 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

Product 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)nicotinamideYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
4 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-7284ce091d0d4d73ab5485e60d960e4a
Source dataset
uspto-grants-2014_09
Patent number
US08822478B2

Reaction notes

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