Water → HCID 66711984, compound

HRID 1262267Notes

Reaction equation

HRID 1262267 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[N:29]2[C:24]([CH:25]=[N:26][C:27]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([N:37]4[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]4)=[CH:33][CH:32]=3)=[N:28]2)=[CH:23][CH:22]=1.CC1(C)C(C)(C)OB([C:52]2[CH:61]=[CH:60][CH:59]=[CH:58][C:53]=2[O:54][CH2:55][C:56]#[N:57])O1.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[CH3:43][N:40]1[CH2:41][CH2:42][N:37]([C:34]2[CH:33]=[CH:32][C:31]([NH:30][C:27]3[N:26]=[CH:25][C:24]4=[CH:23][CH:22]=[C:21]([C:52]5[CH:61]=[CH:60][CH:59]=[CH:58][C:53]=5[O:54][CH2:55][C:56]#[N:57])[N:29]4[N:28]=3)=[CH:36][CH:35]=2)[CH2:38][CH2:39]1

Participants

8

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 17998915[2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]acetonitrileHCID 66711200(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 66711984HCID 66711984, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

Into a 30 mL vial, Palladium Acetate (10 mg, 0.04 mmol), Triphenylphosphine (33 mg, 0.12 mmol) were added. The mixture was purged with nitrogen for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (110.0 mg, 0.2840 mmol), [2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-acetonitrile (0.1472 g, 0.5681 mmol), N,N-Dimethylformamide (2.00 mL) and 1.50 M of Sodium carbonate in Water (2.0 mL, 3.0 mmol) were added. The reaction mixture was heated at 55° C. for 45 minutes. The reaction was partitioned with water and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum. The desired product was isolated via ISCO column chromatography with DCM and methanol as eluant (0 to 15% methanol). The collected fractions afforded (2-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenoxy)-acetonitrile as a yellow solid (65 mg, 52%). LCMS (E/I+) 440.2 (M+H). MP 95-101° C. NMR 1H (DMSO-d6)-9.16 (s, 1H), 8.92 (s, 1H), 7.88-7.98 (m, 1H), 7.48-7.58 (m, 3H), 7.34 (d, 1H, J=9.43), 7.26 (t, 1H, J=8.64 Hz), 6.94 (d, 1H, J=5.50), 6.90 (d, 1H, J=4.70 Hz), 6.81 (d, 2H, J=9.43 Hz), 5.19 (s, 2H), 3.03 (bs 3H), 2.45 (bs, 3H), 2.22 (s, 3H).

Workup

  1. customThe mixture was purged with nitrogen for 10 minutes
  2. customThe reaction was partitioned with water and DCM
  3. customThe organic was separated
  4. washwashed with Brine
  5. dry with materialdried over Na2SO4
  6. filtrationThe solid was filtered
  7. washwashed with DCM
  8. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-7d282f8a64fc4cf992b570d56ebb8a12
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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