7-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amine → HCID 58529670, compound

HRID 1972880Notes

Reaction equation

HRID 1972880 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:28]1[N:36]2[C:31]([C:32]([NH2:37])=[N:33][CH:34]=[N:35]2)=[CH:30][CH:29]=1>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([C:28]3[N:36]4[C:31]([C:32]([NH2:37])=[N:33][CH:34]=[N:35]4)=[CH:30][CH:29]=3)=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 2

HCID 422813837-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 53302321tert-Butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 58529670HCID 58529670, compoundYield 98.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butylester (4 g, 11 mmol) and 7-bromo-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (1.3 g, 6.1 mmol) in DME (133 mL) and 2 N Na2CO3 solution (26 mL) was added Pd(dppf)Cl2 (452 mg, 0.6 mmol). The reaction mixture was degassed with N2 for 15 min. The mixture was heated to 80° C. for 23 h. The reaction mixture was filtered through a pad of Celite® and the filtrate was concentrated in vacuo. The crude residue was purified by Biotage® to provide 2.20 g (55%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.9 (m, 2 H), 7.85 (d, 1 H), 7.2 (d, 1 H), 7.0 (d, 2 H), 4.5 (s, 2 H), 3.5 (t, 2 H), 2.8 (t, 2 H) 1.4 (s, 9 H); ES-MS m/z 366.05 [M+H]+, HPLC RT (min) 2.64.

Workup

  1. customThe reaction mixture was degassed with N2 for 15 min
  2. filtrationThe reaction mixture was filtered through a pad of Celite®
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe crude residue was purified by Biotage®

Sources & evidence

ORD record
ord-19a956df8eff4eddb8f0b2215892d47c
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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