Tetrahydrofuran → HCID 50942990, compound

HRID 2038392Notes

Reaction equation

HRID 2038392 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[S:13][C:12]([C:14](O)=[O:15])=[N:11][C:10]=2[C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([C:24]#[N:25])[CH:18]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.C1CN([P+](ON2N=[N:50][C:45]3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C([N:62](CC)C(C)C)(C)C.[O:68]1CC[CH2:70][CH2:69]1>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[S:13][C:12]([C:14]([N:62]3[CH2:70][C:69](=[O:68])[NH:50][CH2:45]3)=[O:15])=[N:11][C:10]=2[C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([C:24]#[N:25])[CH:18]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 703333745-(3-Chloro-5-fluorophenyl)-4-(3-cyano-4-fluorophenyl)-1,3-thiazole-2-carboxylic acid

Product 1

HCID 50942990HCID 50942990, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

45.0 mg (0.119 mmol) of the compound from Example 30A having a purity of 84%, 26.3 mg (0.131) of the compound from Example 20A and 93.2 mg (0.179 mmol) of PyBOP are provided in 4.8 ml of tetrahydrofuran, and 67 μl (0.382 mmol) of N,N-diisopropylethylamine are added at room temperature. The reaction solution is stirred at room temperature overnight, diluted with dichloromethane and subsequently washed with a 1N aqueous hydrogen chloride solution. The organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure, and the crude product is then purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient). 25.0 mg (56% of theory) of the title compound are obtained.

Workup

  1. washsubsequently washed with a 1N aqueous hydrogen chloride solution
  2. dry with materialThe organic phase is dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customthe crude product is then purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-25efdb714ac74982898362f9566a6515
Source dataset
uspto-grants-2013_11
Patent number
US08575357B2

Reaction notes

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