Water → 7-Amino-2-methyl-4-{1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1H-pyrazol-4-yl}-2,3-dihydro-1H-isoindol-1-one

HRID 511394Notes

Reaction equation

HRID 511394 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5](Br)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2.[O:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]1[O:20][CH2:21][CH2:22][N:23]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[N:24]1.ClCCl.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.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[CH:3]=[CH:4][C:5]([C:26]2[CH:25]=[N:24][N:23]([CH2:22][CH2:21][O:20][CH:15]3[CH2:16][CH2:17][CH2:18][CH2:19][O:14]3)[CH:27]=2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2

Participants

8

Reactant 5

HCID 962WaterHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 534084597-Amino-4-bromo-2-methylisoindolin-1-oneHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 672552857-Amino-2-methyl-4-{1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1H-pyrazol-4-yl}-2,3-dihydro-1H-isoindol-1-one

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of [A] 7-amino-4-bromo-2-methyl-2,3-dihydro-1H-isoindol-1-one (1.0 g, 4.1 mmol), and 1-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole [US 2007265272] (1.6 g, 5.0 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.17 g, 0.21 mmol) in a microwave tube was taken up in 1,4-Dioxane (12 mL). The mixture was treated with a solution of Potassium carbonate (1.7 g, 12 mmol) in H2O (3.0 mL, 170 mmol), flushed with N2, sealed and irradiated in the CEM for 30 minutes at 100° C. Another 1 g of boronic ester was added as well as another 0.05 eq of catalyst. The mixture was sparged with N2, sealed and irradiated for 45 min. This was worked up and purified. 1H NMR (400 MHz, DMSO-d6) δ 1.36-1.50 (m, 4H), 1.57 (td, J=9.22, 3.03 Hz, 1H), 1.63-1.71 (m, 1H), 3.03 (s, 3H), 3.35-3.41 (m, 1H), 3.57 (ddd, J=11.31, 8.40, 3.03 Hz, 1H), 3.75 (dt, J=10.80, 5.34 Hz, 1H), 3.91-3.99 (m, 1H), 4.27-4.33 (m, 2H), 4.44 (s, 2H), 4.55 (t, J=3.28 Hz, 1H), 6.06 (s, 2H), 6.62 (d, J=8.34 Hz, 1H), 7.43 (d, J=8.34 Hz, 1H), 7.74 (d, J=0.51 Hz, 1H), 7.95 (d, J=0.51 Hz, 1H).

Workup

  1. customflushed with N2
  2. customsealed
  3. customirradiated in the CEM for 30 minutes at 100° C
  4. customThe mixture was sparged with N2
  5. customsealed
  6. customirradiated for 45 min
  7. custompurified

Sources & evidence

ORD record
ord-071412a3712446cda963b5f38392bbf5
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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