Pyridine → tert-butyl {2-[[(3-{[5-chloro-4-(3-chloro-5-cyanophenoxy)-1H-1,2,3-benzotriazol-1-yl]methyl}-1H-pyrazolo[3,4-b]pyridin-1-yl)carbonyl](methyl)amino]ethyl}carbamate

HRID 505538Notes

Reaction equation

HRID 505538 reaction equation
[N:1]1[CH:6]=[CH:5]C=C[CH:2]=1.[Cl:7][C:8]1[CH:9]=[C:10]([CH:13]=[C:14]([O:16][C:17]2[C:25]3[N:24]=[N:23][N:22]([CH2:26][C:27]4[C:35]5[C:30](=[N:31][CH:32]=[CH:33][CH:34]=5)[NH:29][N:28]=4)[C:21]=3[CH:20]=[CH:19][C:18]=2[Cl:36])[CH:15]=1)[C:11]#[N:12].Cl[C:38](Cl)([O:40]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(C(C)C)CC)(C)C.[Cl-].[C:59]([O:63][C:64]([NH:66]CC[NH2+]C)=[O:65])([CH3:62])([CH3:61])[CH3:60]>C(Cl)Cl>[Cl:36][C:18]1[CH:19]=[CH:20][C:21]2[N:22]([CH2:26][C:27]3[C:35]4[C:30](=[N:31][CH:32]=[CH:33][CH:34]=4)[N:29]([C:38]([N:1]([CH3:2])[CH2:6][CH2:5][NH:66][C:64](=[O:65])[O:63][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:40])[N:28]=3)[N:23]=[N:24][C:25]=2[C:17]=1[O:16][C:14]1[CH:13]=[C:10]([C:11]#[N:12])[CH:9]=[C:8]([Cl:7])[CH:15]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 178486208HCID 178486208, compoundHCID 178509924HCID 178509924, compound

Product 1

HCID 86624475tert-butyl {2-[[(3-{[5-chloro-4-(3-chloro-5-cyanophenoxy)-1H-1,2,3-benzotriazol-1-yl]methyl}-1H-pyrazolo[3,4-b]pyridin-1-yl)carbonyl](methyl)amino]ethyl}carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Pyridine (0.061 mL, 0.756 mmol) was added to a suspension of 3-chloro-5-{[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-1,2,3-benzotriazol-4-yl]oxy}benzonitrile (165 mg, 0.378 mmol) in DCM (10 mL) at 0° C., followed by the addition in a single charge of triphosgene (45 mg, 0.151 mmol) as a solid, and then by the addition of diisopropyl ethylamine (0.198 mL, 1.135 mmol). This suspension was allowed to stir at 0° C. until a solution was achieved. 2-[(tert-Butoxycarbonyl)amino]-N-methylethanaminium chloride (120 mg, 0.567 mmol) was then added as a solid followed by diisopropyl ethylamine (0.198 mL, 1.135 mmol). The reaction mixture was allowed to warm to room temperature and after 10 minutes, the reaction mixture was diluted with dichloromethane (25 mL), washed with water (15 μL), and the aqueous layer was extracted with dichloromethane (25 mL). The combined organic fractions were dried (MgSO4), filtered and concentrated. The resulting residue was purified by automated column chromatography on silica gel (12 g), eluting with 50-100% EtOAc/hexanes to afford the title compound. LRMS (M+1)=635.6.

Workup

  1. additionfollowed by the addition in
  2. temperatureto warm to room temperature and after 10 minutes
  3. washwashed with water (15 μL)
  4. extractionthe aqueous layer was extracted with dichloromethane (25 mL)
  5. dry with materialThe combined organic fractions were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by automated column chromatography on silica gel (12 g)
  9. washeluting with 50-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-fb08f096919d419dacafae68f0890bd0
Source dataset
uspto-grants-2010_08
Patent number
US07781454B2

Reaction notes

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