Water → HCID 66711405, compound

HRID 1261887Notes

Reaction equation

HRID 1261887 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCOCC1.Br[C:27]1[N:35]2[C:30]([CH:31]=[N:32][C:33]([NH:36][C:37]3[CH:38]=[N:39][C:40]([N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[CH:41][CH:42]=3)=[N:34]2)=[CH:29][CH:28]=1.[Cl:49][C:50]1[CH:51]=[C:52](B(O)O)[CH:53]=[CH:54][CH:55]=1.CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:49][C:50]1[CH:55]=[C:54]([C:27]2[N:35]3[C:30]([CH:31]=[N:32][C:33]([NH:36][C:37]4[CH:38]=[N:39][C:40]([N:43]5[CH2:48][CH2:47][O:46][CH2:45][CH2:44]5)=[CH:41][CH:42]=4)=[N:34]3)=[CH:29][CH:28]=2)[CH:53]=[CH:52][CH:51]=1

Participants

9

Reactant 7

HCID 962WaterHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 2734323(3-Chlorophenyl)boronic acidHCID 66711677HCID 66711677, compound

Product 1

HCID 66711405HCID 66711405, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
85 °C

Procedure

Into a 30 mL vial, Palladium Acetate (12 mg, 0.000053 mol) and Triphenylphosphine (40 mg, 0.0002 mol) were added and purged under an atmosphere of Nitrogen for 10 minutes. 1,4-Dioxane (2.0 mL, 0.026 mol) was added and stirred for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-(6-morpholin-4-yl-pyridin-3-yl)-amine (0.085 g, 0.00023 mol), 3-chlorophenyl boronic acid (0.0712 g, 0.000455 mol), N,N-Dimethylformamide (2.0 mL, 0.026 mol) and 1.50 M of Sodium carbonate in Water (0.842 mL, 0.00126 mol) were added and heated at 85° C. for 8 hours. The reaction was partitioned with DCM. The solid was filtered and washed with DCM. The organic solvent was removed under vacuum. The desired product was isolated via ISCO column chromatography with DCM and methanol as eluant (0 to 10% methanol). The collected fractions afforded [7-(3-Chloro-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(6-morpholin-4-yl-pyridin-3-yl)-amine as a yellow solid. MP 221-222° C. LCMS (E/I+) 407.19 (M+H). NMR 1H (DSMO-d6)-9.29 (s, 1H), 8.98 (s, 1H), 8.41 (d, 1H, J=2.48 Hz), 8.37 (s, 1H), 8.03 (d, 1H, J=7.52 Hz), 7.99 (dd, 2H, JJ=2.68, 6.41 Hz), 7.50 (t, 1H, J=7.88 Hz), 7.40 (d, 1H, J=8.00 Hz), 7.26 (d, 1H, J=4.84 Hz), 6.94 (d, 1H, J=4.74 Hz), 6.86 (d, 1H, J=9.12 Hz), 3.71 (t, 4H, J=4.64 Hz), 3.37 (t, 4H, J=4.92 Hz).

Workup

  1. custompurged under an atmosphere of Nitrogen for 10 minutes
  2. customThe reaction was partitioned with DCM
  3. filtrationThe solid was filtered
  4. washwashed with DCM
  5. customThe organic solvent was removed under vacuum

Sources & evidence

ORD record
ord-b393770618c84734bbfdcd92fff8ab4c
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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