tert-Butyl isocyanate → HCID 118071192, compound

HRID 920841Notes

Reaction equation

HRID 920841 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[C:19]([C:20]([NH2:22])=[O:21])=[C:12]3[CH2:13][NH:14][C:15]4([CH2:18][CH2:17]4)[CH2:16][N:11]3[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[C:23]([N:27]=[C:28]=[O:29])([CH3:26])([CH3:25])[CH3:24]>C1COCC1.O>[C:23]([NH:27][C:28]([N:14]1[C:15]2([CH2:18][CH2:17]2)[CH2:16][N:11]2[N:10]=[C:9]([C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=3)[C:19]([C:20]([NH2:22])=[O:21])=[C:12]2[CH2:13]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]

Participants

5

Reactant 2

HCID 62412tert-Butyl isocyanateHCID 118062734HCID 118062734, compound

Product 1

HCID 118071192HCID 118071192, compoundYield 25.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Intermediate 350H (30 mg, 0.094 mmol) in THF (2 mL) was added TEA (0.026 mL, 0.187 mmol) and tert-butyl isocyanate (0.022 mL, 0.187 mmol) and the resulting solution was stirred at RT for 12 h. The reaction mixture was diluted with water and extracted with EtOAc (3×20 mL). The combined organic layer was washed with brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by preparative HPLC to afford Compound 350 as an off-white solid (10 mg, 25%). HPLC retention times 9.363 min. and 13.023 min. (Methods A and F respectively). MS(ES): m/z=420 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.85 (dd, J=7.31, 2.16 Hz, 1H), 7.68 (ddd, J=8.63, 4.80, 2.20 Hz, 1H), 7.45 (t, J=9 Hz, 1H), 7.30 (br. s, 1H), 7.16 (br. s, 1H), 4.78 (br. s, 2H), 4.10 (br. s, 2H), 1.26 (s, 9H), 1.09 (s, 4H).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated
  6. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-7f529c8b925844a9bafecac2a1af93fa
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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