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2-Amino-4-methylthiazole → 4-[6-[(4-Methyl-1,3-thiazol-2-yl)amino]-2-pyridinyl]morpholin-3-one

HRID 702
Notes
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Reaction equation

HRID 702 reaction equation
Cc1csc(N)n1.O=C1COCCN1c1cccc(Br)n1>CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.Cc1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C([O-])[O-].[Cs+].[Cs+].[Pd]>Cc1csc(Nc2cccc(N3CCOCC3=O)n2)n1
ParticipantsConditionsProcedureSources & evidenceReaction notes

Participants

7

Reactant 2

HCID 741432-Amino-4-methylthiazoleHCID 1343667494-(6-Bromo-2-pyridinyl)morpholin-3-one

Product 1

HCID 1343668134-[6-[(4-Methyl-1,3-thiazol-2-yl)amino]-2-pyridinyl]morpholin-3-oneYield 80.02%

Reagents, catalysts & solvents 4

HCID 10796Cesium carbonateReagent
HCID 636044
1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)
Catalyst
HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst
HCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

**_September 24 2015_** 4-methylthiazol-2-amine (200 mg, 1.75 mmol), 4-(6-bromopyridin-2-yl)morpholin-3-one (450 mg, 1.75 mmol), 4-(6-bromopyridin-2-yl)morpholin-3-one (450 mg, 1.75 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (81 mg, 0.14 mmol) and cesium carbonate (685 mg, 2.10 mmol) in toluene (15 mL) and DMF (1)were microwaved at 115 °C under N2 for one hour. _(Note: Initially, DMF was not added as co-solvent, the microwave instrument was repeatly failed to reach the temperature, and shut down ar 100 °C. It was due to the low thremal absorbance of toluene. Therefore, DMF was added to improve this situation.)_ LCMS showed no precursors and 87% of the desired mass MH+291 @ 0.87 min on a 2-min basic run. The reaction was cooled to RT. **_September 25 2015_** The reaction mixture was diluted with EtOAc, washed with water, filtered, and evaporated to give a brown solid as the crude product. The crude product was added to a silica gel column, and was eluted with 20-100%EtOAc in Heptane. Collected fractions. Based on TLC and LCMS, most product fractions contained a non-MS-ionization unknown, were combined, and evpoarated to give an orange-yellow solid. The orange-yellow solid was reloaded to a silica gel column and was eluted with 20-100%EtOAc in Heptane . Collected fractions . **_September 28 2015_** Based on TLC and LCMS, the product fractions were combined, and evpoarated to give a pale-yellow solid. Based on LCMS, it was 93% pure; based on NMR, it was 94~95% pure.

Sources & evidence

ORD record
ord-4ad2f7e2a41645bd9dba54aaef4fa989
Source dataset
750 AstraZeneca ELN dataset
Original link
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Reaction notes

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