N-methyl-2-pyrrolidone → HCID 25025277, compound

HRID 509980Notes

Reaction equation

HRID 509980 reaction equation
C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[C:13]3[C:12]([CH2:20][C:21]3[CH:22]=[N:23][C:24](S(C)(=O)=O)=[N:25][CH:26]=3)=[CH:11]2)(=O)=O)C=CC=CC=1.CN1CCCC1=O.[F:38][C:39]1[CH:44]=[CH:43][C:42]([C@@H:45]([NH2:47])[CH3:46])=[CH:41][CH:40]=1.[OH-].[K+]>C(O)(=O)C>[Cl:19][C:17]1[CH:18]=[C:13]2[C:12]([CH2:20][C:21]3[CH:26]=[N:25][C:24]([NH:47][C@H:45]([C:42]4[CH:43]=[CH:44][C:39]([F:38])=[CH:40][CH:41]=4)[CH3:46])=[N:23][CH:22]=3)=[CH:11][NH:10][C:14]2=[N:15][CH:16]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 14797Potassium HydroxideHCID 2779063(S)-1-(4-Fluorophenyl)-ethylamineHCID 57619182HCID 57619182, compound

Product 1

HCID 25025277HCID 25025277, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

In a microwave vial, 1-benzenesulfonyl-5-chloro-3-(2-methanesulfonyl-pyrimidin-5-ylmethyl)-1H-pyrrolo[2,3-b]pyridine (132, 12 mg, 0.026 mmol) was mixed with 600 μL of N-methylpyrrolidinone and (S)-1-(4-fluoro-phenyl)-ethylamine (133, 25.2 mg, 0.18 mmol). The reaction was irradiated at 200° C. for 40 minutes in microwave, then potassium hydroxide (500 μL, 4.00 M in water) was added and the reaction irradiated at 90° C. for 10 minutes in microwave. The reaction was neutralized with the addition of 120 μL of acetic acid, solvents were removed under vacuum, and the resulting material was dissolved in 400 μL of dimethyl sulfoxide for purification by HPLC. The desired compound was purified on Phenomenex C18 column (50 mm×10 mm ID) with mobile phase A of 0.1% trifluoroacetic acid in water, mobile phase B of 0.1% trifluoroacetic acid in acetonitrile, 20-100% B over 16 minutes at a flow rate of 6 mL/min. Appropriate fractions were collected and solvents removed under vacuum to provide the desired compound. MS (ESI) [M+H′]′=381.9.

Workup

  1. customThe reaction was irradiated at 200° C. for 40 minutes in microwave
  2. customthe reaction irradiated at 90° C. for 10 minutes in microwave
  3. customwere removed under vacuum
  4. dissolutionthe resulting material was dissolved in 400 μL of dimethyl sulfoxide for purification by HPLC
  5. customThe desired compound was purified on Phenomenex C18 column (50 mm×10 mm ID) with mobile phase A of 0.1% trifluoroacetic acid in water, mobile phase B of 0.1% trifluoroacetic acid in acetonitrile, 20-100% B over 16 minutes at a flow rate of 6 mL/min
  6. customAppropriate fractions were collected
  7. customsolvents removed under vacuum

Sources & evidence

ORD record
ord-daa3e6f4008249d4b168f871f1491027
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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