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

HRID 678
Notes
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Reaction equation

HRID 678 reaction equation
Cc1csc(N)n1.O=C1OCCCN1c1cccc(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(N3CCCOC3=O)n2)n1
ParticipantsConditionsProcedureSources & evidenceReaction notes

Participants

7

Reactant 2

HCID 741432-Amino-4-methylthiazoleHCID 816159873-(6-Bromo-2-pyridinyl)-1,3-oxazinan-2-one

Product 1

HCID 1343668493-[6-[(4-Methyl-1,3-thiazol-2-yl)amino]-2-pyridinyl]-1,3-oxazinan-2-oneYield 43.95%

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
120 °C

Procedure

**_September 21 2015_** 4-methylthiazol-2-amine (85 mg, 0.74 mmol), 3-(6-bromopyridin-2-yl)-1,3-oxazinan-2-one (191 mg, 0.74 mmol), 3-(6-bromopyridin-2-yl)-1,3-oxazinan-2-one (191 mg, 0.74 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.1 mg, 0.07 mmol) and cesium carbonate (291 mg, 0.89 mmol) in toluene (5 mL) were microwaved at 120 °C under N2 for one hour. LCMS showed no precursors and 51% of the desired mass MH+291 @ 0.86 min on a 2-min basic run. 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 Biotage column, and was eluted with 15-100%EtOAc in Heptane. Collected fractions. **_September 22 2015_** Based on TLC and LCMS, the product fractions were combined, and evpoarated to give an yellow-brown solid (94 mg). Based on LCMS, it was only 89% pure. Based on LCMS, it was 96% pure; based on NMR, it was > 95% pure.

Sources & evidence

ORD record
ord-db902466b4d9464996daff204ba92575
Source dataset
750 AstraZeneca ELN dataset
Original link
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Reaction notes

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