Sodium t-butoxide → HCID 178503400, compound

HRID 707374Notes

Reaction equation

HRID 707374 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[N:6]=[C:7]([NH:9][C@H:10]3[CH2:13][C@H:12]([NH2:14])[CH2:11]3)[S:8][C:4]=2[CH:3]=1.Cl[C:18]1[C:23]([C:24]([CH3:31])([CH3:30])[C:25](OCC)=[O:26])=[CH:22][N:21]=[C:20]([S:32][CH3:33])[N:19]=1.C1(P(C2CCCCC2)C2C(OC)=CC=C(OC)C=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>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]>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[N:6]=[C:7]([NH:9][C@H:10]3[CH2:11][C@H:12]([N:14]4[C:22]5[N:21]=[C:20]([S:32][CH3:33])[N:19]=[CH:18][C:23]=5[C:24]([CH3:30])([CH3:31])[C:25]4=[O:26])[CH2:13]3)[S:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 23676156Sodium t-butoxideHCID 25112535BrettphosHCID 86694234Ethyl 2-(4-chloro-2-(methylthio)pyrimidin-5-yl)-2-methylpropanoateHCID 178511739HCID 178511739, compound

Product 1

HCID 178503400HCID 178503400, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Following the procedure described for Example 44 (MethOD B6), using trans-N1-(6-fluorobenzo[d]thiazol-2-yl)cyclobutane-1,3-diamine, INTERMEDIATE 72 (0.454 g, 1.913 mmol), ethyl 2-(4-chloro-2-(methylthio)pyrimidin-5-yl)-2-methylpropanoate (0.550 g, 2.002 mmol), dicyclohexyl(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (0.185 g, 0.344 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.131 g, 0.143 mmol), sodium t-butoxide (0.460 g, 4.78 mmol) in dry dioxane (3 mL) afforded the title 7-(trans-3-((6-fluorobenzo[d]thiazol-2-yl)amino)cyclobutyl)-5,5-dimethyl-2-(methylthio)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (0.230 g, 0.535 mmol, 28.0% yield). m/z: 430.1 (M+1); 1H NMR (400 MHz, CHLOROFORM-d) δ: ppm 1.41 (s, 6H) 2.42-2.53 (m, 2 H) 2.61 (s, 3H) 3.38-3.53 (m, 2 H) 4.55-4.65 (m, 1 H) 5.15-5.27 (m, 1 H) 5.91 (br s, 1 H) 7.03 (td, J=9.0 Hz, 2.6 Hz, 1H) 7.32 (dd, J=8.2 Hz, 2.6 Hz, 1H) 7.49 (dd, J=8.9 Hz, 4.7 Hz, 1H) 8.12 (s, 1H).

Sources & evidence

ORD record
ord-6613a3f81f084212b014c41e6dec7b69
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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