Sodium Carbonate → methyl 3-(7-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

HRID 1410068Notes

Reaction equation

HRID 1410068 reaction equation
[C@@H:1]12[O:8][C@@H:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[CH:10]=[C:11]([NH:15][C:16]3[C:17]4[N:25]=[CH:24][S:23][C:18]=4[N:19]=[C:20](Cl)[N:21]=3)[CH:12]=[CH:13][CH:14]=1)[CH2:2]2.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([CH:41]=[CH:42][CH:43]=2)[C:37]([O:39][CH3:40])=[O:38])O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[C@@H:1]12[O:8][C@@H:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[CH:10]=[C:11]([NH:15][C:16]3[C:17]4[N:25]=[CH:24][S:23][C:18]=4[N:19]=[C:20]([C:34]4[CH:35]=[C:36]([CH:41]=[CH:42][CH:43]=4)[C:37]([O:39][CH3:40])=[O:38])[N:21]=3)[CH:12]=[CH:13][CH:14]=1)[CH2:2]2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27346513-Methoxycarbonylphenylboronic acid pinacol esterHCID 86671786N-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenyl)-5-chlorothiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 68379578methyl 3-(7-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoateYield 78.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The mixture of N-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenyl)-5-chlorothiazolo[5,4-d]pyrimidin-7-amine (0.095 g, 0.254 mmol), methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (0.073 g, 0.28 mmol), Pd (PPh3)4 (0.015 g, 0.013 mmol) and Na2CO3 (0.081 g, 0.762 mmol) in dioxane (20 mL) and H2O (5 mL) was heated to 100° C. for 16 h under N2 atmosphere. Then it was concentrated to dryness. The residue was purified by column chromatography (silica gel, 200˜300 mesh, eluting with ethyl acetate:petroleum ether=1:2) to afford methyl 3-(7-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (0.094 g, 78%) as a yellow solid. LC-MS: 474 [M+H]+, tR=1.84 min.

Workup

  1. concentrationThen it was concentrated to dryness
  2. customThe residue was purified by column chromatography (silica gel, 200˜300 mesh, eluting with ethyl acetate:petroleum ether=1:2)

Sources & evidence

ORD record
ord-96d758511eb3404085654408bcc2a8ca
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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