Sodium hydride → HCID 58204078, compound

HRID 1849369Notes

Reaction equation

HRID 1849369 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[S:23][C:22]3[C:21]4[N:24]=[C:25]([NH2:28])[CH:26]=[CH:27][C:20]=4[O:19][CH2:18][CH2:17][C:16]=3[CH:15]=2)=[N:12][CH:11]=[N:10]1.[H-].[Na+].BrC[CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35]>C1COCC1>[C:37]([O:36][C:34](=[O:35])[CH2:33][NH:28][C:25]1[CH:26]=[CH:27][C:20]2[O:19][CH2:18][CH2:17][C:16]3[CH:15]=[C:14]([C:13]4[N:9]([C:3]5[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=5[F:1])[N:10]=[CH:11][N:12]=4)[S:23][C:22]=3[C:21]=2[N:24]=1)([CH3:40])([CH3:39])[CH3:38]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 256128tert-Butyl 3-bromopropionateHCID 58204142HCID 58204142, compound

Product 1

HCID 58204078HCID 58204078, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Compound 134 (800 mg, 2.0 mmol) was dissolved in THF (20 mL). It was stirred at 0° C. and NaH (58 mg, 2.4 mmol) was added. Then the mixture was warmed to r.t. and stirred for further 0.5 h. The mixture was cooled to 0° C. and tert-butyl 3-bromopropanoate (502 mg, 2.4 mmol) was added. Later, it was warmed to 80° C. for 2 h. The reaction mixture was filtered to gather the solution. Then water was added into the solution. It was extracted by DCM (20 mL×3). The combined organics were dried over Na2SO4, concentrated in vacuo, and separated by prep TLC (DCM) to give {2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulen-9-ylamino}-acetic acid tert-butyl ester (900 mg, yield: 90%) 1HNMR (CDCl3, 400 MHz): δ 8.04 (s, 1 H), 7.45-7.52 (m, 1 H), 7.42 (s, 1H), 7.06-6.93 (m, 4H). 4.25-4.15 (m, 2H), 4.08-3.99 (m, 2H), 3.06 (s, 2H), 1.38 (s, 9H). LC-MS (ESI): m/z=512 [M+H]+

Workup

  1. temperatureThen the mixture was warmed to r.t.
  2. stirringstirred for further 0.5 h
  3. temperatureThe mixture was cooled to 0° C.
  4. temperatureLater, it was warmed to 80° C. for 2 h
  5. filtrationThe reaction mixture was filtered
  6. additionThen water was added into the solution
  7. extractionIt was extracted by DCM (20 mL×3)
  8. dry with materialThe combined organics were dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customseparated by prep TLC (DCM)

Sources & evidence

ORD record
ord-c33f8da2b65141979d35abb875796403
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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