Tetrahydrofuran → HCID 17751814, compound

HRID 1091511Notes

Reaction equation

HRID 1091511 reaction equation
C[O-].[Na+].C1COCC1.C1(C)C(S([CH2:18][N+:19]#[C-:20])(=O)=O)=CC=CC=1.[NH2:22][C:23]1[C:28]2=[C:29]([C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41]([NH:43][C:44]4[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][N:45]=4)=[O:42])=[C:36]([F:54])[CH:35]=3)[CH:30]=[C:31]([CH:32]=[O:33])[N:27]2[N:26]=[CH:25][N:24]=1>CO.CCOC(C)=O>[NH2:22][C:23]1[C:28]2=[C:29]([C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41]([NH:43][C:44]4[CH:49]=[C:48]([C:50]([F:52])([F:51])[F:53])[CH:47]=[CH:46][N:45]=4)=[O:42])=[C:36]([F:54])[CH:35]=3)[CH:30]=[C:31]([C:32]3[O:33][CH:20]=[N:19][CH:18]=3)[N:27]2[N:26]=[CH:25][N:24]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10942334Sodium MethoxideHCID 17751813HCID 17751813, compoundHCID 53627694Toluenesulfonylmethyl isocyanide

Product 1

HCID 17751814HCID 17751814, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of sodium methoxide in MeOH (25% by wt, 211 mg, 0.98 mmol) was taken up in MeOH (2 mL) and THF (8 mL) and the solution cooled to 0° C. Toluenesulfonylmethylisocyanide (96.6 mg, 0.49 mmol) and N-[4-(4-amino-7-formylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-N′-[4-(trifluoromethyl)pyridin-2-yl]urea (150 mg, 0.33 mmol) were added in succession to the solution. The reaction was stirred at 0° C. for 5 min, then heated at 60° C. for 1 h. The reaction was cooled to rt and diluted with EtOAc (100 mL). The organic layer was wash with water (2×) and dried with sodium sulfate. The suspension was filtered and the filtrate concentrated in vacuo. The resulting solid was triturated with ether, and subsequently with THF to provide the title compound (67 mg, 41%) as a tan solid. 1H-NMR (DMSO-d6) δ 9.43 (s, 1H), 9.30 (s, 1H), 8.65 (dd, 1H), 8.31 (t, 1H), 8.17 (s, 1H), 7.52 (t, 1H), 7.37-7.46 (m, 2H), 7.26-7.32 (m, 1H), 7.23 (m, 1H); MS [M+H]+=499.1; LCMS RT=3.00 min.

Workup

  1. temperatureheated at 60° C. for 1 h
  2. temperatureThe reaction was cooled to rt
  3. washThe organic layer was wash with water (2×)
  4. dry with materialdried with sodium sulfate
  5. filtrationThe suspension was filtered
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe resulting solid was triturated with ether

Sources & evidence

ORD record
ord-d6d9f4f108ba49a0857287133f54a011
Source dataset
uspto-grants-2012_03
Patent number
US08129379B2

Reaction notes

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