Sodium Carbonate → (S)-4-(5-(3-fluoro-4-(2-morpholinoethoxy)phenyl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine

HRID 1478573Notes

Reaction equation

HRID 1478573 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.[F:30][C:31]1[CH:45]=[C:44](B2OC(C)(C)C(C)(C)O2)[CH:43]=[CH:42][C:32]=1[O:33][CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[F:30][C:31]1[CH:45]=[C:44]([C:2]2[CH:3]=[N:4][C:5]([N:8]3[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][N:15]4[C:19]5=[N:20][C:21]([C:24]6[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=6)=[CH:22][N:23]=[C:18]5[N:17]=[N:16]4)[CH2:9]3)=[N:6][CH:7]=2)[CH:43]=[CH:42][C:32]=1[O:33][CH2:34][CH2:35][N:36]1[CH2:37][CH2:38][O:39][CH2:40][CH2:41]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 73507291HCID 73507291, compoundHCID 1317365094-(2-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenoxy)ethyl)morpholine

Product 1

HCID 118364799(S)-4-(5-(3-fluoro-4-(2-morpholinoethoxy)phenyl)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholineYield 40%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °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 15 mg (0.033 mmol) was dissolved in dioxane 1 ml, and 4-(2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenoxy)ethyl)morpholine 17 mg (0.049 mmol) and 1M sodium carbonate 98.4 ul (0.098 mmol) were added. Pd(PPh3)4 2 mg (0.0016 mmol) was added, and the mixture was purged with N2 (g), followed by stirring at 105° C. for 4 hours. When the reaction was completed, the reaction mixture was extracted with ethyl acetate and brine, and the organic layer was dried over Na2SO4. Prep LC with 4% MeOH/MC gave a product 7.8 mg (40%).

Workup

  1. customthe mixture was purged with N2 (g)
  2. extractionthe reaction mixture was extracted with ethyl acetate and brine
  3. dry with materialthe organic layer was dried over Na2SO4

Sources & evidence

ORD record
ord-222052855fbb4c2b9030509a599630f6
Source dataset
uspto-grants-2016_08
Patent number
US09403831B2

Reaction notes

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