Potassium Phosphate, Tribasic → (1S,3R)-N1-(5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)-N3-(pyrazin-2-yl)cyclohexane-1,3-diamine

HRID 75053Notes

Reaction equation

HRID 75053 reaction equation
[BH4-].[Na+].Cl[C:4]1[CH:5]=[C:6]2[C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11][N:10](S(C3C=CC(C)=CC=3)(=O)=O)[C:7]2=[N:8][CH:9]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.ClC1C=C2C(C3N=C(S(C)=O)C([F:93])=CN=3)=CN(S(C3C=CC(C)=CC=3)(=O)=O)C2=NC=1.CC[N:106]([CH:110](C)C)C(C)C.Cl[C:114]1[N:119]=[C:118]([NH:120][C@H:121]2[CH2:126][CH2:125][CH2:124][C@@H:123]([NH:127][C:128]([N:130]3[CH2:134][CH2:133][C@@H](F)C3)=O)[CH2:122]2)[C:117]([F:136])=[CH:116][N:115]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1.CC#N.O.CO>[F:136][C:117]1[C:118]([NH:120][C@H:121]2[CH2:126][CH2:125][CH2:124][C@@H:123]([NH:127][C:128]3[CH:110]=[N:106][CH:133]=[CH:134][N:130]=3)[CH2:122]2)=[N:119][C:114]([C:12]2[C:6]3[C:7](=[N:8][CH:9]=[C:4]([F:93])[CH:5]=3)[NH:10][CH:11]=2)=[N:115][CH:116]=1

Participants

14

Reactant 7

HCID 62657Potassium Phosphate, TribasicHCID 81531Diisopropylethylamine2×HCID 4311764Sodium borohydrideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 575977475-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine2×HCID 672853215-Chloro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridineHCID 86719751(R)-N-((1R,3S)-3-((2-chloro-5-fluoropyrimidin-4-yl)amino)cyclohexyl)-3-fluoropyrrolidine-1-carboxamide

Product 1

HCID 68008579(1S,3R)-N1-(5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)-N3-(pyrazin-2-yl)cyclohexane-1,3-diamine

Reagents, catalysts & solvents 6

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

NaBH4, MeOH; (b) 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine, 2-Me-THF, water, K3PO4, Pd(PPh3)4, XPhos, Tris(dibenzylideneacetone)dipalladium, reflux; (c) bis(2,5-dioxopyrrolidin-1-yl) carbonate, iPr2NEt, CH3CN; (d) (3R)-3-fluoropyrrolidine, iPr2NEt, CH3CN (e) 2N LiOH, THF.

Sources & evidence

ORD record
ord-6140d402d4e0403a82537d816846490a
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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