Cesium carbonate → HCID 90040984, compound

HRID 523029Notes

Reaction equation

HRID 523029 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:11]([C:12]([NH:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:10][N:9]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]2=[N:6][C:7]=1[Cl:8].Cl.[CH3:28][C:29]1[CH:33]=[C:32]([NH2:34])[S:31][N:30]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:15]([NH:14][C:12]([C:11]1[C:4]2[C:5](=[N:6][C:7]([Cl:8])=[C:2]([NH:34][C:32]3[S:31][N:30]=[C:29]([CH3:28])[CH:33]=3)[N:3]=2)[N:9]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:10]=1)=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 90040556HCID 90040556, compound

Product 1

HCID 90040984HCID 90040984, compoundYield 17.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-bromo-N-tert-butyl-3-chloro-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (125 mg, 271 μmol), 3-methylisothiazol-5-amine hydrochloride (61.2 mg, 406 μmol), Pd2(dba)3 (24.8 mg, 27.1 μmol), xantphos (47.0 mg, 81.2 μmol) and cesium carbonate (265 mg, 812 μmol) in dioxane (1.5 mL) was heated in a microwave at 150° C. for 20 min. Pd2(dba)3 (24.8 mg, 27.1 μmol) and xantphos (47.0 mg, 81.2 μmol) were added and continued to heat in a microwave at 150° C. for 30 min. The mixture was cooled then filtered through a pad of celite. The filtrate was concentrated in vacuo then purified by chromatography (silica, 10-50% ethyl acetate in hexanes) to give N-tert-butyl-3-chloro-2-(3-methylisothiazol-5-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (40 mg, 48.5 μmol, 17.9%) as brown gum. (EI/CI) m/z: 495.1 [M+H].

Workup

  1. temperatureto heat in a microwave at 150° C. for 30 min
  2. temperatureThe mixture was cooled
  3. filtrationthen filtered through a pad of celite
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthen purified by chromatography (silica, 10-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-7b4f73ae408549e4b47e83876944730e
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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