trans-2-Phenyl-1-cyclopropanecarbonyl chloride → HCID 90693417, compound

HRID 432524Notes

Reaction equation

HRID 432524 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:20][C:21]3([OH:34])[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[C:13]([O:18][CH3:19])[CH:12]=3)[C:3]=12.[C:35]1([C@@H:41]2[CH2:43][C@H:42]2[C:44](Cl)=[O:45])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>N1C=CC=CC=1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:20][C:21]3([OH:34])[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[CH2:25][CH2:26]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:44]([C@@H:42]4[CH2:43][C@H:41]4[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[O:45])=[C:13]([O:18][CH3:19])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 13656trans-2-Phenyl-1-cyclopropanecarbonyl chlorideHCID 22347381tert-butyl 4-{[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl}-4-hydroxy-1-piperidinecarboxylate

Product 1

HCID 90693417HCID 90693417, compoundYield 76.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-5 °C

Procedure

To a mixture of tert-butyl 4-{[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl}-4-hydroxy-1-piperidinecarboxylate (0.08 g, 0.00017 mol) in pyridine (4 mL) was added trans-2-phenyl-cyclopropane carbonyl chloride (0.035g, 0.00019 mol) at −5° C. The mixture was stirred at −5° C. for 10 minutes then warmed up to room temperature to stir for 1 hours. The mixture was quenched with an aqueous 1N solution of sodium hydroxide. Pyridine was removed under reduced pressure. The residue was partitioned between water and dichloromethane (50 mL). The organic layer was washed with water. The solvents were removed under reduced and the residue was purified by RP-HPLC (Hypersilprep HS C18, 8μm, 250×21.1 mm; 5%-100% over 35 min with 0.1 M ammonium acetate, 21 mL/min) to yield trans tert-butyl 4-{[4-amino-3-(3-methoxy-4-{[(2-phenylcyclopropyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl}-4-hydroxy-1-piperidinecarboxylate (0.08 g, 0.00013 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 10.7 min. MS: MH+ 614.

Workup

  1. temperaturethen warmed up to room temperature
  2. stirringto stir for 1 hours
  3. customThe mixture was quenched with an aqueous 1N solution of sodium hydroxide
  4. customPyridine was removed under reduced pressure
  5. customThe residue was partitioned between water and dichloromethane (50 mL)
  6. washThe organic layer was washed with water
  7. customThe solvents were removed
  8. customthe residue was purified by RP-HPLC (Hypersilprep HS C18, 8μm, 250×21.1 mm; 5%-100% over 35 min with 0.1 M ammonium acetate, 21 mL/min)

Sources & evidence

ORD record
ord-f44536f351f646da93c583356707c3d6
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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