Potassium Iodide → tert-Butyl 3-{3-[1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-fluoro-2-methoxyphenyl}azetidine-1-carboxylate

HRID 1499750Notes

Reaction equation

HRID 1499750 reaction equation
[Cl:1][C:2]1[C:3]([F:24])=[C:4]([CH:13]2[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]2)[C:5]([O:11][CH3:12])=[C:6]([CH:8](Cl)[CH3:9])[CH:7]=1.[I:25][C:26]1[C:34]2[C:29](=[N:30][CH:31]=[N:32][C:33]=2[NH2:35])[NH:28][N:27]=1.[I-].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.CCOC(C)=O>[NH2:35][C:33]1[N:32]=[CH:31][N:30]=[C:29]2[N:28]([CH:8]([C:6]3[C:5]([O:11][CH3:12])=[C:4]([CH:13]4[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]4)[C:3]([F:24])=[C:2]([Cl:1])[CH:7]=3)[CH3:9])[N:27]=[C:26]([I:25])[C:34]=12

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 86666861Tert-butyl 3-(3-chloro-5-(1-chloroethyl)-2-fluoro-6-methoxyphenyl)azetidine-1-carboxylate2×HCID 178508725HCID 178508725, compound

Product 1

HCID 86677679tert-Butyl 3-{3-[1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-fluoro-2-methoxyphenyl}azetidine-1-carboxylateYield 45.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
140 °C

Procedure

To a mixture of tert-butyl 3-[3-chloro-5-(1-chloroethyl)-2-fluoro-6-methoxyphenyl]azetidine-1-carboxylate (0.77 g, 2.0 mmol, racemic intermediate from Example 13, Step 6), 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.58 g, 2.2 mmol) in N,N-dimethylformamide (6.9 mL) was added potassium iodide (34 mg, 0.20 mmol) and cesium carbonate (0.99 g, 3.0 mmol). The resulting mixture was heated at 140° C. and stirred for 3 h. After cooling, the clear solution was taken into water and ethyl acetate (EtOAc). The solid was diluted with water and EtOAc, and stirred until dissolved. The organic layers were combined, concentrated and purified on silica gel (eluting with 0 to 100% EtOAc in hexanes) to give the desired product (0.55 g, 45%). LCMS calculated for C22H26ClFN6O3 (M+H)+: m/z=603.1; Found: 602.9.

Workup

  1. temperatureAfter cooling
  2. stirringstirred
  3. dissolutionuntil dissolved
  4. concentrationconcentrated
  5. custompurified on silica gel (eluting with 0 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-89dc369a2df440ecbfeaea14594dd853
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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