Pyrrolidine → HCID 90417260, compound

HRID 710000Notes

Reaction equation

HRID 710000 reaction equation
[CH3:1][O:2][C:3]1[C:8]([C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)[CH:18]=3)=[CH:11][N:10]=2)=[CH:7][N:6]=[C:5](SC)[N:4]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.[NH:42]1[CH2:46][CH2:45][CH2:44][CH2:43]1>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:8]([C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)[CH:18]=3)=[CH:11][N:10]=2)=[CH:7][N:6]=[C:5]([N:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)[N:4]=1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 70297m-Chloroperbenzoic acidHCID 90417835HCID 90417835, compound

Product 1

HCID 90417260HCID 90417260, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-methoxy-5-(4-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyri-dine-2-yl)-2-(methylthio)pyrimidine (0.28 g, 0.67 mmol) in DCM (10 mL) was treated with mCPBA (0.20 g, 0.80 mmol), stirred at RT for 3 h, treated with pyrrolidine (0.50 mL, 6.1 mmol) and stirred at RT overnight. The mixture was treated with satd. NaHCO3, extracted with DCM (3×) and the combined organics were dried over MgSO4, concentrated to dryness and purified by silica gel chromatography (MeOH/DCM) to afford 4-methoxy-5-(4-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-(pyrrolidin-1-yl)pyrimidine (0.19 g, 64%). 1H NMR (400 MHz, DMSO-d6): δ 8.76 (s, 1H), 8.37 (s, 1H), 8.35 (d, J=5.7 Hz, 1H), 8.27 (s, 1H), 7.97 (s, 1H), 7.85 (s, 1H), 7.25 (d, J=2.4 Hz, 1H), 6.60 (dd, J=5.7, 2.5 Hz, 1H), 4.00 (s, 3H), 3.84 (s, 3H), 3.55 (s, 5H), 2.18 (s, 3H), 1.93-1.92 (m, 4H); MS (ESI) m/z: 444.2 (M+H+).

Workup

  1. stirringstirred at RT overnight
  2. additionThe mixture was treated with satd
  3. extractionNaHCO3, extracted with DCM (3×)
  4. dry with materialthe combined organics were dried over MgSO4
  5. concentrationconcentrated to dryness
  6. custompurified by silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-ad589e5fe3994446947c7dd2ffe75710
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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