2-Methyl-1H-imidazole-4-carboxylic acid → HCID 59507070, compound

HRID 1800684Notes

Reaction equation

HRID 1800684 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[N:5]=[C:6]([N:11]([CH3:32])[C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:31])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=4)[CH:15]=[CH:16][CH:17]=3)[N:7]=[CH:8][C:9]=2[N:10]=1.[CH3:33][C:34]1[NH:35][C:36]([C:39](O)=[O:40])=[CH:37][N:38]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>N1C=CC=CC=1>[C:29]([C:26]([C:22]1[CH:21]=[C:20]([C:19]([NH:18][C:14]2[CH:13]=[C:12]([N:11]([CH3:32])[C:6]3[N:7]=[CH:8][C:9]4[N:10]=[C:2]([NH:1][C:39]([C:36]5[NH:35][C:34]([CH3:33])=[N:38][CH:37]=5)=[O:40])[S:3][C:4]=4[N:5]=3)[CH:17]=[CH:16][CH:15]=2)=[O:31])[CH:25]=[CH:24][CH:23]=1)([CH3:27])[CH3:28])#[N:30]

Participants

6

Reactant 4

HCID 738242-Methyl-1H-imidazole-4-carboxylic acidHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86646073HCID 86646073, compound

Product 1

HCID 59507070HCID 59507070, compoundYield 65.4%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-d]pyrimidin-5-yl)(methyl)amino]phenyl}-3-(1-cyano-1-methylethyl)benzamide (150 mg, 338 μmol) produced in Example D5(i) in pyridine (4 mL) were added 2-methyl-1H-imidazole-5-carboxylic acid (146 mg, 1.01 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (770 mg, 2.03 mmol), and the mixture was stirred at 90° C. for 20 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (15 mL), and the mixture was extracted with ethyl acetate (20 mL, 10 mL). The combined organic layer was washed with saturated brine (5 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→90/10), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from tetrahydrofuran and methanol to give the title compound (122 mg, 65%) as colorless crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (20 mL, 10 mL)
  2. washThe combined organic layer was washed with saturated brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→90/10)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from tetrahydrofuran and methanol

Sources & evidence

ORD record
ord-7990cc3ec4774933a0bb99bfe92b21a8
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

Loading…