Sodium Carbonate → HCID 58529337, compound

HRID 1972882Notes

Reaction equation

HRID 1972882 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([C:18]3[N:26]4[C:21]([C:22]([NH2:27])=[N:23][CH:24]=[N:25]4)=[C:20](Br)[CH:19]=3)=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:37]2[CH:38]=[CH:39][C:40]3[C:44]([CH:45]=2)=[N:43][NH:42][CH:41]=3)O1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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:18]3[N:26]4[C:21]([C:22]([NH2:27])=[N:23][CH:24]=[N:25]4)=[C:20]([C:37]4[CH:38]=[CH:39][C:40]5[C:44]([CH:45]=4)=[N:43][N:42]([CH2:9][C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)[CH:41]=5)[CH:19]=3)=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58529321HCID 58529321, compoundHCID 178431020HCID 178431020, compound

Product 1

HCID 58529337HCID 58529337, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 7-(4-amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.2 g, 2.7 mmol) in DMF (20 mL), 2-benzyl- was added 6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (1.4 g, 4.3 mmol), Pd(dppf)Cl2 (311 mg, 0.27 mmol) and 2 N Na2CO3 solution (12 mL). The mixture was degassed with N2 for 20 min. The reaction was irradiated in a microwave reactor at 150° C. for 10 min. After cooling, the mixture was partitioned between EtOAc and H2O, The organic layer was separated and dried over Na2SO4. Biotage® chromatography (50-100% EtOAc/hexane) provided the title product as off white solid, 1.1 g (71%). 1H NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1 H), 8.05 (d, 2 H), 8.0 (s, 1 H), 7.90 (d, 1 H), 7.70 (s, 1 H), 7.60-7.40 (m, 7 H), 7.25 (d, 1 H), 7.20 (s, 1 H), 5.70 (s, 2 H), 4.6 (m, 2 H), 3.6 (m, 2 H), 2.80 (m, 2 H), 1.4 (m, 9 H); ES-MS m/z 572.24 [M+H]+, HPLC RT (min) 3.44.

Workup

  1. customThe mixture was degassed with N2 for 20 min
  2. customThe reaction was irradiated in a microwave reactor at 150° C. for 10 min
  3. temperatureAfter cooling
  4. customthe mixture was partitioned between EtOAc and H2O
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-bba3e865f5f1414ead72016300f86542
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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