HCID 58529663, compound → HCID 58529448, compound

HRID 1972972Notes

Reaction equation

HRID 1972972 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8](Br)[CH:9]=[C:10]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.[CH2:25]([N:32]1[CH:40]=[C:39]2[C:34]([CH:35]=[C:36](B3OC(C)(C)C(C)(C)O3)[C:37]([F:41])=[CH:38]2)=[N:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][CH:11]([C:10]2[N:6]3[C:7]([C:2]([NH2:1])=[N:3][CH:4]=[N:5]3)=[C:8]([C:36]3[C:37]([F:41])=[CH:38][C:39]4[C:34]([CH:35]=3)=[N:33][N:32]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:40]=4)[CH:9]=2)[CH2:12][CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

3

Reactant 2

HCID 58529663HCID 58529663, compoundHCID 59231971HCID 59231971, compound

Product 1

HCID 58529448HCID 58529448, compoundYield 90.8%

Procedure

To the microwave vial was added tert-butyl 4-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)piperidine-1-carboxylate (250 mg, 0.63 mmol), 2-benzyl-5-fluoro-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (300 mg, 0.85 mmol, 1.35 eq), and tetrakis(trephenylphosphine)palladium (0) (46 mg, 0.063 mmol, 0.1 eq). Degassed, anhydrous DMF (6.3 mL) was added followed by 2.0M sodium carbonate solution (1.0 mL). The vial was capped and the reaction was irradiated in a microwave reactor at 180° C. for 25 min. The mixture was cooled to rt, diluted with EtOAc and filtered through a pad of Celite® to remove excess palladium. The filtrate was washed with 50% aqueous brine (3×), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by ISCO® (gradient elution 0 to 10% MeOH/DCM) to give the product (309.7 mg, 68%) as an oil. 1H-NMR (300 MHz, CD3OD) 8.35 (s, 1H), 7.84 (s, 1H), 7.63 (d, 1H), 7.56 (d, 1H), 7.38 to 7.31 (m, 5H), 6.59 (s, 1H), 5.65 (s, 2H), 4.23 to 4.17 (m, 2H), 3.48 to 3.39 (m, 1H), 2.95 (broad s, 2H), 2.12 (d, 2H), 1.72 to 1.59 (m, 2H), 1.47 (s, 9H); ES-MS m/z 542.3 [M+H]+, RT (min) 3.10.

Workup

  1. customDegassed
  2. additionanhydrous DMF (6.3 mL) was added
  3. customThe vial was capped
  4. customthe reaction was irradiated in a microwave reactor at 180° C. for 25 min
  5. additiondiluted with EtOAc
  6. filtrationfiltered through a pad of Celite®
  7. customto remove excess palladium
  8. washThe filtrate was washed with 50% aqueous brine (3×)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by ISCO® (gradient elution 0 to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-ed89082edb364e0c8b5564d212e7b10f
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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