Dichloromethane → HCID 58529316, compound

HRID 1972791Notes

Reaction equation

HRID 1972791 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8](Br)[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][OH:14])[N:6]2[N:5]=[CH:4][N:3]=1.[CH2:16]([N:23]1[CH:31]=[C:30]2[C:25]([CH:26]=[C:27](B3OC(C)(C)C(C)(C)O3)[CH:28]=[CH:29]2)=[N:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.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]>[NH2:1][C:2]1[C:7]2=[C:8]([C:27]3[CH:28]=[CH:29][C:30]4[C:25]([CH:26]=3)=[N:24][N:23]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:31]=4)[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][OH:14])[N:6]2[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 59231966HCID 59231966, compound

Product 1

HCID 58529316HCID 58529316, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
80 °C

Procedure

3-(4-Amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-propan-1-ol (4.0 g, 14.75 mmol) and 2-benzyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (6.66 g, 19.9 mmol, 1.35 eq) were dissolved in 1:1 v/v EtOH-toluene and degassed with nitrogen. After 30 minutes [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (1.20 g, 1.47 mmol, 0.1 eq) followed by 2M sodium carbonate solution (22 mL, 44.26 mmol, 3.0 eq) were added. The reaction mixture was stirred at 80° C. for 6 h. The reaction mixture was partitioned between EtOAc and water and filtered through a pad of Celite® to rid of excess palladium salts. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated at reduced pressure. The crude product was purified by MPLC eluted with 10% MeOH/DCM with 1% Et3N to give the desired product as white foam (3.41 g, 58%). 1H-NMR (DMSO-d6) 8.53 (s, 1H), 7.87 (s, 1H), 7.78 (d, 1H), 7.57 (s, 1H), 7.28 to 7.35 (m, 5H), 7.13 (d, 1H), 6.58 (s, 1H), 5.64 (s, 2H), 4.53 (t, 1H), 3.47 (q, 2H), 2.91 (t, 2H), 1.82 to 1.86 (m, 2H); LC-MS [M+H]P=399, RT=2.41 min.

Workup

  1. customdegassed with nitrogen
  2. additionwere added
  3. customThe reaction mixture was partitioned between EtOAc and water
  4. filtrationfiltered through a pad of Celite®
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated at reduced pressure
  9. customThe crude product was purified by MPLC
  10. washeluted with 10% MeOH/DCM with 1% Et3N

Sources & evidence

ORD record
ord-5cbbb0cd35834388a3253b3188b082a9
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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