2-(1-((2-Chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol → HCID 53377616, compound

HRID 2091920Notes

Reaction equation

HRID 2091920 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:5]2[N:11]=[C:10]([CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([C:19]([OH:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]3)[CH:9]=[CH:8][C:6]=2[N:7]=1.C([Sn](CCCC)(CCCC)[C:34]1[N:39]2[N:40]=[CH:41][N:42]=[C:38]2[CH:37]=[CH:36][CH:35]=1)CCC>C1COCC1.[Cu]I.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>[N:42]1[CH:41]=[N:40][N:39]2[C:34]([C:2]3[N:3]=[C:4]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[C:5]4[N:11]=[C:10]([CH2:12][N:13]5[CH2:18][CH2:17][CH:16]([C:19]([OH:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]5)[CH:9]=[CH:8][C:6]=4[N:7]=3)=[CH:35][CH:36]=[CH:37][C:38]=12

Participants

6

Reactant 2

HCID 584049702-(1-((2-Chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-olHCID 67342552HCID 67342552, compound

Product 1

HCID 53377616HCID 53377616, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
140 °C

Procedure

2-(1-((2-Chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol from Example 8 (50 mg, 0.12 mmol) was dissolved in 2 mL of THF and treated with CuI (1.2 mg, 0.006 mmol) and 5-(tributylstannyl)-[1,2,4]triazolo[1,5-a]pyridine (65.4 mg, 0.16 mmol). The solution was sparged with bubbling nitrogen and tetrakis(triphenylphosphine)palladium (0) (7 mg, 0.006 mmol) was added. The mixture was heated in an Agilent microwave (140° C., 20 min). The solution was cooled to room temperature and concentrated. Purification by reverse phase HPLC gave 166 as a colorless solid. 1H NMR (400 MHz, DMSO) δ 8.52 (s, 1H), 8.21 (d, J=8.6 Hz, 1H), 7.99 (d, J=8.9 Hz, 1H), 7.91 (d, J=8.7 Hz, 1H), 7.84-7.74 (m, 1H), 7.65 (d, J=7.0 Hz, 1H), 4.51 (s, 4H), 4.03 (s, 1H), 3.83-3.77 (m, 4H), 3.75 (s, 2H), 2.93 (d, J=11.1 Hz, 2H), 2.00 (t, J=11.2 Hz, 2H), 1.67 (d, J=11.4 Hz, 2H), 1.24 (overlapping m, 3H), 1.04 (s, 6H). LCMS: 489.2

Workup

  1. additionwas added
  2. temperatureThe solution was cooled to room temperature
  3. concentrationconcentrated
  4. customPurification by reverse phase HPLC

Sources & evidence

ORD record
ord-7dd3991c2ad74ddda84f6ea86d1deeac
Source dataset
uspto-grants-2013_05
Patent number
US08440651B2

Reaction notes

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