Ammonia → (2'-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3-indol]-1'(2'H)-yl)acetamide

HRID 1407887Notes

Reaction equation

HRID 1407887 reaction equation
[O:1]=[C:2]1[C:10]2([CH2:14][O:13][C:12]3[CH:15]=[C:16]4[C:20](=[CH:21][C:11]2=3)[CH2:19][CH2:18][O:17]4)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:22][C:23](O)=[O:24].N.O1CCOCC1.F[P-](F)(F)(F)(F)F.[N:40]1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(#N)C.C(N(CC)CC)C>[O:1]=[C:2]1[C:10]2([CH2:14][O:13][C:12]3[CH:15]=[C:16]4[C:20](=[CH:21][C:11]2=3)[CH2:19][CH2:18][O:17]4)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:22][C:23]([NH2:40])=[O:24]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 312751,4-DioxaneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59263485(2'-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3-indol]-1'(2'H)-yl)acetic acid

Product 1

HCID 59352622(2'-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3-indol]-1'(2'H)-yl)acetamideYield 24.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of (2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)acetic acid (0.25 g, 0.74 mmol), triethylamine (0.5 mL), ammonia in dioxane (0.5M, 4.5 mL, 2.3 mmol) in acetonitrile (10 mL) was added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.33 g, 0.9 mmol). The solution was stirred at ambient temperature for 18 h then concentrated in vacuo to dryness. The residue was dissolved in ethyl acetate (50 mL) and washed with 2 M sodium carbonate (2×25 mL) and 1 M hydrochloric acid (2×25 mL). The ethyl acetate layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to dryness. Recrystallization from diethyl ether (25 mL) in a Branson ultrasonic bench top water bath afforded 2-(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)acetamide (0.06 g, 23%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ 7.66 (s, 1H), 7.29-7.21 (m, 2H), 7.10 (d, J=6.5 Hz, 1H), 7.03-6.90 (m, 2H), 6.55 (s, 1H), 6.36 (s, 1H), 4.72 (ABq, 2H), 4.53-4.38 (m, 1H), 4.29 (ABq, 2H), 2.92 (t, J=8.6 Hz, 2H); MS (ES+) m/z 337.1 (M+1), 359.1 (M+23).

Workup

  1. concentrationthen concentrated in vacuo to dryness
  2. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  3. washwashed with 2 M sodium carbonate (2×25 mL) and 1 M hydrochloric acid (2×25 mL)
  4. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to dryness
  7. customRecrystallization from diethyl ether (25 mL) in a Branson ultrasonic bench top water bath

Sources & evidence

ORD record
ord-c995fcf3fc7f4a169e7963683b89be65
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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