Toluene → HCID 57786649, compound

HRID 1969113Notes

Reaction equation

HRID 1969113 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([CH:28]=[CH:29][N:30]=2)[CH:5]=[C:6]([C:8]2[C:9]([CH3:27])=[C:10]([NH:14][C:15](=[O:26])[C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:18][CH:17]=3)[CH:11]=[CH:12][CH:13]=2)[CH:7]=1.[CH:31]([N:34]([CH:37](C)C)CC)(C)C.C(Cl)(Cl)=[O:41].C1(C)C=CC=CC=1.CN.C1COCC1>ClCCl>[C:22]([C:19]1[CH:20]=[CH:21][C:16]([C:15]([NH:14][C:10]2[CH:11]=[CH:12][CH:13]=[C:8]([C:6]3[CH:7]=[C:2]([NH:1][C:31]([NH:34][CH3:37])=[O:41])[C:3]4[N:4]([CH:28]=[CH:29][N:30]=4)[CH:5]=3)[C:9]=2[CH3:27])=[O:26])=[CH:17][CH:18]=1)([CH3:25])([CH3:23])[CH3:24]

Participants

8

Reactant 6

HCID 1140TolueneHCID 6329MethylamineHCID 6371PhosgeneHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 42643655HCID 42643655, compound

Product 1

HCID 57786649HCID 57786649, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To N-[3-(8-Amino-imidazo[1,2-a]pyridin-6-yl)-2-methyl-phenyl]-4-tert-butyl-benzamide (120 mg, 0.3 mmol) in dichloromethane (10 mL) was added diisopropylethylamine (0.13 mL, 2.5 eq). The resulting mixture was cooled to 0° C. and with stirring was added a solution of 20% phosgene in toluene (0.94 mL, 6 eq), and this solution was stirred at 0° C. for 30 minutes. Next, a 2.0M solution of methylamine in THF (3 mL, 20 eq) was added and the resulting mixture was stirred from 0° C. to room temperature overnight. The next day the solvent was removed under reduced pressure at 55° C. and then added ethyl acetate (35 mL) and water (25 mL). The layers were partitioned and then separated and the organic layer was dried over magnesium sulfate, filtered, and concentrated. The crude material was purified by Preparative Thin Layer Chromatography eluting with 50% acetone in hexanes to give the title compound as an off-white powder (47 mg), ((M+H)+=456).

Workup

  1. stirringthis solution was stirred at 0° C. for 30 minutes
  2. stirringthe resulting mixture was stirred from 0° C. to room temperature overnight
  3. customThe next day the solvent was removed under reduced pressure at 55° C.
  4. customThe layers were partitioned
  5. customseparated
  6. dry with materialthe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by Preparative Thin Layer Chromatography
  10. washeluting with 50% acetone in hexanes

Sources & evidence

ORD record
ord-4772915e91ff40209466d8e011953fd6
Source dataset
uspto-grants-2013_04
Patent number
US08426441B2

Reaction notes

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