Water → 6,6-Dimethyl-2-[6-(pyrimidin-5-yl)-2,3-dihydrobenzo[1,4]oxazin-4-yl]-6,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

HRID 885962Notes

Reaction equation

HRID 885962 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:11]3[S:12][C:13]4[CH2:14]C(C)(C)N[C:17](=O)[C:18]=4[N:19]=3)[C:6]=2[CH:23]=1.[N:24]1[CH:29]=[C:28](B(O)O)[CH:27]=[N:26][CH:25]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[OH2:41]>COCCOC.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>[CH3:5][C:6]1([CH3:23])[NH:7][C:14](=[O:41])[C:13]2[S:12][C:11]([N:7]3[C:6]4[CH:23]=[C:2]([C:28]5[CH:29]=[N:24][CH:25]=[N:26][CH:27]=5)[CH:3]=[CH:4][C:5]=4[O:10][CH2:9][CH2:8]3)=[N:19][C:18]=2[CH2:17]1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 685972362-(6-Bromo-2,3-dihydrobenzo[1,4]oxazin-4-yl)-6,6-dimethyl-6,7-dihydro-[1,3]thiazolo[5,4-d]pyridin-4(5h)-one

Product 1

HCID 671857046,6-Dimethyl-2-[6-(pyrimidin-5-yl)-2,3-dihydrobenzo[1,4]oxazin-4-yl]-6,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-4(5h)-oneYield 6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of Example 39 (0.135 g, 0.34 mmol), 5-pyrimidinylboronic acid (0.084 g, 0.68 mmol), K3PO4 (0.143 g, 0.68 mmol), water (1 mL) and tetrakis(triphenylphosphine)palladium(0) (catalytic) in DME (5 mL) was heated to 120° C. under microwave irradiation for 30 minutes. After cooling to r.t. the reaction mixture was filtered and purified by preparative HPLC (Method 7) to give the title compound (0.008 g, 6%) as a pale yellow solid. δH (CD3OD) 9.12 (1H, s), 9.01 (2H, s), 8.44 (1H, d, J 2.3 Hz), 7.40 (1H, dd, J 8.5 and J 2.3 Hz), 7.14 (1H, d, J 8.5 Hz), 4.47-4.40 (2H, m), 4.21-4.14 (2H, m), 2.92 (2H, s), 1.41 (6H, s). Exchangeable proton was not observed. LCMS (ES+) 393.0 (M)+, RT 2.83 minutes (Method 2).

Workup

  1. filtrationwas filtered
  2. custompurified by preparative HPLC (Method 7)

Sources & evidence

ORD record
ord-b316995f741e4906a304e5f289ff0ab0
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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