Dimethylformamide → (2-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanol

HRID 1262407Notes

Reaction equation

HRID 1262407 reaction equation
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.B1(O)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH2:27][O:26]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.C(Cl)Cl.CO>[CH3:24][N:21]1[CH2:22][CH2:23][N:18]([C:15]2[CH:14]=[CH:13][C:12]([NH:11][C:8]3[N:7]=[CH:6][C:5]4=[CH:4][CH:3]=[C:2]([C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=5[CH2:27][OH:26])[N:10]4[N:9]=3)=[CH:17][CH:16]=2)[CH2:19][CH2:20]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 4037881-Hydroxy-2,1-benzoxaboroleHCID 66711200(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 66712560(2-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanolYield 75%

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (88 mg, 0.23 mmol), 3H-Benzo[c][1,2]oxaborol-1-ol (74 mg, 0.56 mmol), Cesium Carbonate (192 mg, 0.589 mmol) and Bis(tri-tert-butylphosphine)palladium (18 mg, 0.035 mmol) were placed in a vial. N,N-Dimethylformamide (4.0 mL, 52 mmol) was added to the mixture, which was “degassed” under vacuum with cooling on dry ice. The mixture was then heated in an 85° C. block under an atmosphere of Nitrogen for 2 h, then conc. in vacuo. The residue was purified on ISCO (24 g load cartridge with DCM:MeOH, then dried; 12 g column, 0-15% MeOH:DCM) to afford (2-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanol (71 mg; Yield=75%) as an orange foam. LCMS (HPLC): 0.75 min, 415 (M+H); 1H-NMR (DMSO-d6): 9.18 (s, 1H), 8.94 (s, 1H), 7.68 (d, 1H, J=7.5 Hz), 7.63 (d, 1H, J=7.5 Hz), 7.48 (m, 3H), 7.43 (m, 1H), 6.92 (d, 1H, J=4.5 Hz), 6.88 (d, 1H, J=4.5 Hz), 6.74 (d, 2H, J=9.0 Hz), 5.11 (t, 1H, J=5.3 Hz), 4.45 (d, 2H, J=5.3 Hz), 3.01 (m, 4H), 2.44 (m, 4H), 2.22 (s, 3H).

Workup

  1. customdegassed” under vacuum
  2. temperaturewith cooling on dry ice
  3. customThe residue was purified on ISCO (24 g load cartridge with DCM
  4. dry with materialMeOH, then dried

Sources & evidence

ORD record
ord-3f5cc282f0714382a2292bcbcf7a3549
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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