Potassium Carbonate → (S)-tert-butyl 4-(2-(2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholino)pyrimidin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1478571Notes

Reaction equation

HRID 1478571 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][N:15]3[C:19]4=[N:20][C:21]([C:24]5[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=5)=[CH:22][N:23]=[C:18]4[N:17]=[N:16]3)[CH2:9]2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:38]2[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH:39]=2)O1.C(=O)([O-])[O-].[K+].[K+]>COCOC.O.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]>[CH3:29][N:27]1[CH:28]=[C:24]([C:21]2[N:20]=[C:19]3[N:15]([CH2:14][C@@H:10]4[CH2:9][N:8]([C:5]5[N:4]=[CH:3][C:2]([C:38]6[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH:39]=6)=[CH:7][N:6]=5)[CH2:13][CH2:12][O:11]4)[N:16]=[N:17][C:18]3=[N:23][CH:22]=2)[CH:25]=[N:26]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 73507291HCID 73507291, compound

Product 1

HCID 118364759(S)-tert-butyl 4-(2-(2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholino)pyrimidin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 78.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8020DimethoxymethaneSolvent

Conditions

Temperature
80 °C

Procedure

(S)-4-(5-bromopyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine 500 mg (1.09 mmol) was dissolved in dimethoxymethane 8 ml, and then tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate 406 mg (1.31 mol) was added. Potassium carbonate 453 mg (3.28 mmol) was dissolved in distilled water 2 ml, which was then added to the reaction solution. PdCl2(dppf)2 45 mg (0.0547 mmol) was added, and the mixture was purged with N2 (g), followed by stirring at 80° C. for 2 hours. After the completion of the reaction, the reaction mixture was extracted with ethyl acetate and brine, and the organic layer was dried over Na2SO4. 3% MeOH/MC chromatography gave a product 478 mg (78%).

Workup

  1. additionwhich was then added to the reaction solution
  2. customthe mixture was purged with N2 (g)
  3. customAfter the completion of the reaction
  4. extractionthe reaction mixture was extracted with ethyl acetate and brine
  5. dry with materialthe organic layer was dried over Na2SO4

Sources & evidence

ORD record
ord-c51c9b6443624fd1a26ed854b0466be7
Source dataset
uspto-grants-2016_08
Patent number
US09403831B2

Reaction notes

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