Potassium Phosphate, Tribasic → 4-[5-(Cyclopropylmethoxy)-2-methylsulfonylpyrimidin-4-yl]-2-methyl-5,6,7,8-tetrahydroisoquinolin-1-one

HRID 575651Notes

Reaction equation

HRID 575651 reaction equation
[CH3:1][N:2]1[CH:11]=[C:10](B2OC(C)(C)C(C)(C)O2)[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[C:3]1=[O:21].Cl[C:23]1[C:28]([O:29][CH2:30][CH:31]2[CH2:33][CH2:32]2)=[CH:27][N:26]=[C:25]([S:34]([CH3:37])(=[O:36])=[O:35])[N:24]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1.O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CC(=O)OCC>[CH:31]1([CH2:30][O:29][C:28]2[C:27]([C:10]3[C:9]4[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=4[C:3](=[O:21])[N:2]([CH3:1])[CH:11]=3)=[N:26][C:25]([S:34]([CH3:37])(=[O:35])=[O:36])=[N:24][CH:23]=2)[CH2:32][CH2:33]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 218864351,4-Dioxane--water (1/1)HCID 1180224454-Chloro-5-(cyclopropylmethoxy)-2-methylsulfonylpyrimidineHCID 1238019002-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6,7,8-tetrahydroisoquinolin-1-one

Product 1

HCID 1180219724-[5-(Cyclopropylmethoxy)-2-methylsulfonylpyrimidin-4-yl]-2-methyl-5,6,7,8-tetrahydroisoquinolin-1-oneYield 67%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

The title compound of step 3 (200 mg, 0.69 mmol), the title compound of Example 152, step 4 (218 mg, 0.83 mmol), K3PO4 (440 mg, 2.07 mmol) and Pd(dppf)Cl2 (51 mg, 0.7 mmol) in 6:1 dioxane/water (7 mL) were purged with nitrogen and heated at 70° C. for 8 h. After silica gel chromatography (PE:EA=1:1), the title compound (180 mg, yield: 67%) was obtained as a light yellow solid. 1H NMR (CDCl3, 400 MHz): δ 8.42 (s, 1H), 7.48 (s, 1H), 4.04 (d, J=7.2 Hz, 2H), 3.60 (s, 3H), 3.35 (s, 3H), 2.65-2.62 (m, 2H), 2.54-2.50 (m, 2H), 1.80-1.78 (m, 2H), 1.77-1.67 (m, 2H), 1.28-1.25 (m, 1H), 0.73-0.71 (m, 2H), 0.41-0.38 (m, 2H).

Sources & evidence

ORD record
ord-b9342e73ef8b453a92c329a98f0a7ce4
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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