Hydrochloric Acid → 2-(4-{4-[7-(4-Dimethylaminomethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamide

HRID 1262393Notes

Reaction equation

HRID 1262393 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:42]=[CH:41][C:40]([CH:43]4[CH2:48][CH2:47][N:46]([CH2:49][C:50]([NH2:52])=[O:51])[CH2:45][CH2:44]4)=[CH:39][CH:38]=3)=[N:34]2)=[CH:29][CH:28]=1.[CH3:53][N:54]([CH3:71])[CH2:55][C:56]1[CH:61]=[CH:60][C:59](B2OC(C)(C)C(C)(C)O2)=[CH:58][CH:57]=1.Cl.C(=O)([O-])[O-].[Na+].[Na+].O.O1CCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:53][N:54]([CH2:55][C:56]1[CH:61]=[CH:60][C:59]([C:27]2[N:35]3[C:30]([CH:31]=[N:32][C:33]([NH:36][C:37]4[CH:42]=[CH:41][C:40]([CH:43]5[CH2:48][CH2:47][N:46]([CH2:49][C:50]([NH2:52])=[O:51])[CH2:45][CH2:44]5)=[CH:39][CH:38]=4)=[N:34]3)=[CH:29][CH:28]=2)=[CH:58][CH:57]=1)[CH3:71]

Participants

10

Reactant 8

HCID 313Hydrochloric AcidHCID 962WaterHCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 34604594-((N,N-Dimethylamino)methyl)phenylboronic acid pinacol esterHCID 667107962-{4-[4-(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino)-phenyl]-piperidin-1-yl}-acetamide

Product 1

HCID 573979652-(4-{4-[7-(4-Dimethylaminomethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamide

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

Palladium Acetate (8.5 mg, 0.000038 mol), Triphenylphosphine (27.4 mg, 0.000105 mol) and 1,4-Dioxane (2.8 mL, 0.036 mol) were combined in a flask and stirred for 10 minutes. 2-{4-[4-(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino)-phenyl]-piperidin-1-yl}-acetamide (157 mg, 0.000366 mol), Dimethyl-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-benzyl]-amine; hydrochloride (224 mg, 0.000753 mol), and 1.50 M of Sodium carbonate in Water (2.2 mL, 0.0033 mol) and Tetrahydrofuran (3.0 mL, 0.037 mol). were added. The reaction was heated at 80° C. for 3 days, then purified by preparatory HPLC and lyophilized to yield an orange solid, 2-(4-{4-[7-(4-Dimethylaminomethyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamide; compound with 3 trifluoroacetic acids (4 mg, 1%). LCMS: m/z=484.18 (M+H+); 1H NMR (400 MHz, DMSO-d6) δ 9.95 (br s, 1H), 9.55 (m, 2H), 9.02 (s, 1H), 8.33 (d, 2H, J=8.2 Hz), 8.00 (m, 1H), 7.73 (m, 3H), 7.65 (m, 3H), 7.28 (d, 1H, J=4.8 Hz), 7.18 (d, 2H, J=8.4 Hz), 6.99 (d, 1H, J=4.8 Hz), 4.36 (m, 2H), 3.94 (m, 2H), 3.16 (m, 2H), 2.75 (m, 7H), 1.99 (m, 4H), 1.30 (s, 2H).

Workup

  1. additionwere added
  2. custompurified by preparatory HPLC

Sources & evidence

ORD record
ord-9691ba4f57a64ef6baacc5bfd6123394
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…