Potassium Phosphate, Tribasic → HCID 67959805, compound

HRID 1529452Notes

Reaction equation

HRID 1529452 reaction equation
[CH3:1][O:2][C:3]1[CH:45]=[CH:44][C:6]([CH2:7][O:8][C:9]2[N:14]=[C:13]([S:15]([CH3:18])(=[O:17])=[O:16])[N:12]=[C:11]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25](B5OC(C)(C)C(C)(C)O5)[CH:26]=4)[N:21]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH:20]=3)[CH:10]=2)=[CH:5][CH:4]=1.Br[C:47]1[CH:52]=[N:51][CH:50]=[C:49]([CH:53]2[CH2:55][CH2:54]2)[N:48]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C>[CH:53]1([C:49]2[N:48]=[C:47]([C:25]3[CH:26]=[C:27]4[C:22](=[CH:23][CH:24]=3)[N:21]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[CH:20]=[C:19]4[C:11]3[CH:10]=[C:9]([O:8][CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:45][CH:44]=4)[N:14]=[C:13]([S:15]([CH3:18])(=[O:17])=[O:16])[N:12]=3)[CH:52]=[N:51][CH:50]=2)[CH2:55][CH2:54]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 457883052-Bromo-6-cyclopropylpyrazineHCID 67959744HCID 67959744, compound

Product 1

HCID 67959805HCID 67959805, compoundYield 28.4%

Reagents, catalysts & solvents 3

HCID 178482226HCID 178482226, compoundCatalystHCID 6344DichloromethaneSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with tert-butyl 3-(6-(4-methoxybenzyloxy)-2-(methylsulfonyl)pyrimidin-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (150 mg, 0.236 mmol) and 2-bromo-6-cyclopropylpyrazine (70.5 mg, 0.354 mmol, CombiPhos) in p-dioxane/H2O (4:1, 2.0 mL) followed by potassium phosphate (100 mg, 0.472 mmol) and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (8.36 mg, 0.012 mmol). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 20 min. The mixture was diluted with DCM and washed with water. The organic layer was dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 20-60% EtOAc in hexanes) to give tert-butyl 5-(6-cyclopropylpyrazin-2-yl)-3-(6-(4-methoxybenzyloxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1H-indole-1-carboxylate (42 mg, 0.067 mmol, 28.3% yield) as a solid: MS (ESI, pos. ion) m/z: 628.0 (M+1), and 5-(6-cyclopropylpyrazin-2-yl)-3-(6-(4-methoxybenzyloxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1H-indole (28 mg, 0.053 mmol, 22.49% yield) as a solid. MS (ESI, pos. ion) m/z: 528.0 (M+1).

Workup

  1. customA glass microwave reaction vessel
  2. washwashed with water
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel chromatography (eluting with 20-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2beafe6cf24e4f08bba14d4b26dc9041
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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