Pyridine → HCID 69460412, compound

HRID 1157423Notes

Reaction equation

HRID 1157423 reaction equation
ClC(Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.C[CH2:14][N:15]([CH:19](C)C)[CH:16]([CH3:18])C.[CH3:22][N:23](CCNC)[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27].[Cl:35][C:36]1[CH:37]=[C:38]([CH:41]=[C:42]([O:44][C:45]2[CH:50]=[C:49]([O:51][CH2:52][C:53]3[C:61]4[C:56](=[N:57][CH:58]=[CH:59][CH:60]=4)[NH:55][N:54]=3)[CH:48]=[CH:47][C:46]=2[Cl:62])[CH:43]=1)[C:39]#[N:40].N1C=CC=CC=1>C(Cl)Cl>[Cl:62][C:46]1[CH:47]=[CH:48][C:49]([O:51][CH2:52][C:53]2[C:61]3[C:56](=[N:57][CH:58]=[CH:59][CH:60]=3)[N:55]([C:14]([N:15]([CH3:19])[CH2:16][CH2:18][N:23]([CH3:22])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:4])[N:54]=2)=[CH:50][C:45]=1[O:44][C:42]1[CH:41]=[C:38]([C:39]#[N:40])[CH:37]=[C:36]([Cl:35])[CH:43]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 14403871tert-Butyl methyl(2-(methylamino)ethyl)carbamateHCID 178509956HCID 178509956, compound

Product 1

HCID 69460412HCID 69460412, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
70 °C

Procedure

To a solution of triphosgene (63 mg, 0.212 mmol) in CH2Cl2 (3 mL) at 0° C. was added a mixture of Hunig's base (0.305 mL, 1.75 mmol) and tert-butyl methyl[2-(methylamino)ethyl]carbamate (100 mg, 0.531 mmol) in CH2Cl2 (2 mL) was added over 2 mins. Five minutes after the addition was complete, the reaction was allowed to warn to room temperature. The 3-chloro-5-[2-chloro-5-(1H-pyrazolo[3,4-b]pyridin-3-ylmethoxy)phenoxy]benzonitrile ((218 mg, 0.531 mmol) and then pyridine (0.141 mL 1.75 mmol) were added at room temperature and the resulting slurry heated at 70° C. in a sealed tube. A pale yellow solution was obtained which was heated at 70° C. for 16 hours. The reaction mixture was cooled to room temperature and the solvents evaporated in vacuo. The residue was dissolved in DMF (4 mL) and purified by reverse phase HPLC using a gradient elution 5 to 95% acetonitrile in water containing 0.1% trifluoroacetic acid. The pure fractions were lyophilized to afford the title compound as a cream solid. MH+-BOC 524. 1H NMR (400 MHz) CDCl3 8.70 (1H, dd, j−4.7 and 1.5 Hz), 8.25 (1H, dd, J=1.4, 8.1 Hz), 7.42 (1H, d, J=8.9 Hz), 7.34 (1H, t, J=1.5 Hz), 7.3291H, dd, J=8.0 and 4.7 Hz), 7.14 (1H, t, J=2 Hz), 7.01 (1H, m), 6.95 (1H, dd, J=8.9 and 2.9 Hz), 6.80 (1H, d, J=2.9 Hz), 3.80-2.60 (10H, m), 1.60-1.30 (9H, m).

Workup

  1. additionwas added over 2 mins
  2. additionFive minutes after the addition
  3. customto warn to room temperature
  4. customA pale yellow solution was obtained which
  5. temperaturewas heated at 70° C. for 16 hours
  6. temperatureThe reaction mixture was cooled to room temperature
  7. customthe solvents evaporated in vacuo
  8. dissolutionThe residue was dissolved in DMF (4 mL)
  9. custompurified by reverse phase HPLC
  10. washa gradient elution 5 to 95% acetonitrile in water containing 0.1% trifluoroacetic acid

Sources & evidence

ORD record
ord-e7fd70911aca4892a08feef5ed68840b
Source dataset
uspto-grants-2010_10
Patent number
US07807684B2

Reaction notes

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