Trifluoroacetic acid → HCID 45280282, compound

HRID 422858Notes

Reaction equation

HRID 422858 reaction equation
[O:1]=[C:2]1[C:10]2([C:14]3=[CH:15][C:16]4[O:20][CH2:19][O:18][C:17]=4[CH:21]=[C:13]3[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C@@H:30]2[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]2)=[CH:25][CH:24]=1.FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl>[NH:32]1[CH2:33][CH2:34][C@@H:30]([NH:29][C:26]2[CH:25]=[CH:24][C:23]([CH2:22][N:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[C:10]4([C:14]5=[CH:15][C:16]6[O:20][CH2:19][O:18][C:17]=6[CH:21]=[C:13]5[O:12][CH2:11]4)[C:2]3=[O:1])=[CH:28][CH:27]=2)[CH2:31]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 45280281HCID 45280281, compound

Product 1

HCID 45280282HCID 45280282, compoundYield 79.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (3R)-3-({4-[(2′-oxospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-1′(2′H)-yl)methyl]phenyl}-amino)pyrrolidine-1-carboxylate (0.53 g, 0.94 mmol) and trifluoroacetic acid (1 mL) in dichloromethane (5 mL) was stirred at ambient temperature for 70 min. The reaction was made basic with 1 M sodium hydroxide (50 mL) and extracted with dichloromethane (4×30 mL). The combined organic solution was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash column chromatography with dichloromethane/methanol/ammonium hydroxide (14:1:0.15) afforded 1′-{4-[(3R)-pyrrolidin-3-ylamino]benzyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.34 g, 78%) as an off-white solid: mp 118-121° C. (hexanes); 1H NMR (300 MHz, CDCl3) δ 7.23-7.13 (m, 4H), 7.00 (dd, J=7.5, 7.5 Hz, 1H), 6.86 (d, J=7.8 Hz, 1H), 6.55 (d, J=8.4 Hz, 2H), 6.52 (s, 1H), 6.12 (s, 1H), 5.87 (d, J=1.2 Hz, 1H), 5.85 (d, J=1.2 Hz, 1H), 4.99-4.94 (m, 2H), 4.71-4.66 (m, 2H), 3.94-3.85 (m, 1H), 3.83 (br s, 1H), 3.15-3.04 (m, 2H), 2.97-2.88 (m, 1H), 2.83 (dd, J=11.1, 3.0 Hz, 1H), 2.21-2.09 (m, 1H), 1.98 (br s, 1H), 1.67-1.57 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 177.6, 155.9, 148.8, 147.2, 142.3, 132.3, 128.85, 128.80, 124.3, 123.8, 123.3, 119.6, 113.4, 109.6, 103.1, 101.5, 93.6, 80.5, 58.3, 53.9, 53.6, 45.7, 43.8, 33.6; MS (ES+) m/z 456.2 (M+1).

Workup

  1. extractionextracted with dichloromethane (4×30 mL)
  2. dry with materialThe combined organic solution was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography with dichloromethane/methanol/ammonium hydroxide (14:1:0.15)

Sources & evidence

ORD record
ord-34fb0cd92d6640df8777a83bf7346d4d
Source dataset
uspto-grants-2012_01
Patent number
US08101647B2

Reaction notes

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