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

HRID 1262402Notes

Reaction equation

HRID 1262402 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.[OH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C)C=O.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:24][N:21]1[CH2:20][CH2:19][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:30]5[CH:31]=[CH:32][C:27]([CH2:26][OH:25])=[CH:28][CH:29]=5)[N:10]4[N:9]=3)=[CH:17][CH:16]=2)[CH2:23][CH2:22]1

Participants

9

Reactant 7

HCID 962WaterHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 66711200(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 66712479(4-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanolYield 81.4%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
90 °C

Procedure

(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.125 g, 0.323 mmol), (4-Hydroxymethylphenyl)boronic acid (98.1 mg, 0.646 mmol), Triphenylphosphine (24 mg, 0.090 mmol) and Palladium Acetate (7.2 mg, 0.032 mmol) were placed in a vial and purged with vac/N2. N,N-Dimethylformamide (10.0 mL, 129 mmol), 1,4-Dioxane (3.0 mL, 38 mmol) and 2.00 M of Sodium carbonate in Water (1.50 mL, 3.00 mmol) were added and the mixture again purged (vac/N2) before being heated to 90° C. for 4 h. HPLC showed complete consumption of s.m. and LCMS showed m/z=415. Cool and partition between water:DCM (1:1, 60 mL). Sept., ext. aq. with 30 mL DCM. Wash comb. org. with brine (30 mL) and dry (sodium sulfate), filt. and conc. Chromatograph residue on ISCO (DCM load, 0-15% MeOH:DCM, 2×12 g silica) to afford (4-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanol (109 mg; Yield=81.5). LCMS (HPLC): 0.73 min, m/z=415 (M+H); 1H-NMR (DMSO-d6): 9.20 (s, 1H), 8.92 (s, 1H), 8.17 (d, 2H, J=8.2 Hz), 7.63 (d, 2H, J=9.0 Hz), 7.47 (d, 2H, J=8.2 Hz), 7.15 (d, 1H, J=4.8 Hz), 6.92 (m, 3H), 5.25 (t, 1H, J=5.8 Hz), 4.58 (d, 2H, J=5.8 Hz), 3.09 (m, 4H), 2.47 (m, 4H), 2.23 (s, 3H).

Workup

  1. custompurged with vac/N2
  2. customthe mixture again purged (vac/N2)
  3. customconsumption of s.m
  4. temperatureCool
  5. custompartition between water:DCM (1:1, 60 mL)
  6. washWash comb
  7. dry with materialwith brine (30 mL) and dry (sodium sulfate), filt

Sources & evidence

ORD record
ord-ab422c3d3a3e406c9be3ff45342ad297
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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