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

HRID 68929Notes

Reaction equation

HRID 68929 reaction equation
[CH:1]1([CH2:4][NH:5][C:6](=[O:43])[C:7]2[CH:12]=[C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18](C3CCCCO3)[N:17]=[C:16]4[C:28]3[NH:42][C:31]4[CH:32]=[N:33][CH:34]=[C:35]([C:36]5[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=5)[C:30]=4[N:29]=3)[CH:10]=[N:9][CH:8]=2)[CH2:3][CH2:2]1.[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]1([CH2:4][NH:5][C:6](=[O:43])[C:7]2[CH:12]=[C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][N:17]=[C:16]4[C:28]3[NH:42][C:31]4[CH:32]=[N:33][CH:34]=[C:35]([C:36]5[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=5)[C:30]=4[N:29]=3)[CH:10]=[N:9][CH:8]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 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)nicotinamide

Product 1

HCID 136055449N-(cyclopropylmethyl)-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1H-indazol-5-yl)nicotinamideYield 45.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 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) (125 mg, 0.22 mmol) and Et3SiH (87 μL, 0.55 mmol) in DCM (5 mL) was slowly added TFA (2.5 mL). The reaction was stirred at r.t. for 3 h. The reaction was evaporated under vacuum and the residue was treated with water, basified with aq. ammonia. The solids were filtered, washed with cold water and dried. The crude product was heated in MeOH and filtered hot to remove impurities. The hot MeOH solution was allowed to slowly cool to r.t. to produce N-(cyclopropylmethyl)-5-(3-(7-(pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-2-yl)-1H-indazol-5-yl)nicotinamide (3) as a off-white solid (48 mg, 0.10 mmol, 44% yield). 1H NMR (DMSO-d6) δ ppm 0.28 (d, J=4.28 Hz, 2H), 0.42-0.58 (m, 2H), 1.09 (br s, 1H), 3.25 (t, J=6.06 Hz, 2H), 7.50-7.70 (m, 1H), 7.79-8.11 (m, 2H), 8.48-8.68 (m, 1H), 8.69-8.82 (m, 1H), 8.81-8.97 (m, 3H), 9.00-9.18 (m, 2H), 9.46 (br s, 1H); ESIMS found C28H22N8O m/z 487 (M+H).

Workup

  1. customThe reaction was evaporated under vacuum
  2. additionthe residue was treated with water
  3. filtrationThe solids were filtered
  4. washwashed with cold water
  5. customdried
  6. temperatureThe crude product was heated in MeOH
  7. filtrationfiltered hot
  8. customto remove impurities
  9. temperatureto slowly cool to r.t.

Sources & evidence

ORD record
ord-1902b70b36cb4f3893734d6d69180562
Source dataset
uspto-grants-2014_09
Patent number
US08822478B2

Reaction notes

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