Cyclopropylamine → N-(1-methylethyl)-2-[(2'-oxospiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-1'(2'H)-yl)methyl]-1,3-oxazole-4-carboxamide

HRID 1965766Notes

Reaction equation

HRID 1965766 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[O:24][CH:25]=[C:26]([C:28]([OH:30])=O)[N:27]=1.O[N:32]1[C:36]2[CH:37]=CC=C[C:35]=2N=N1.C1(N)CC1>ClCCl>[CH3:35][CH:36]([NH:32][C:28]([C:26]1[N:27]=[C:23]([CH2:22][N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]3([C:14]4=[CH:15][C:16]5[O:20][CH2:19][O:18][C:17]=5[CH:21]=[C:13]4[O:12][CH2:11]3)[C:2]2=[O:1])[O:24][CH:25]=1)=[O:30])[CH3:37]

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 686017222-((2'-oxo-6H-spiro[benzofuro[6,5-d][1,3]dioxole-7,3'-indoline]-1'-yl)methyl)oxazole-4-carboxylic acid

Product 1

HCID 68599323N-(1-methylethyl)-2-[(2'-oxospiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-1'(2'H)-yl)methyl]-1,3-oxazole-4-carboxamideYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-((2′-oxo-6H-spiro[benzofuro[6,5-d][1,3]dioxole-7,3′-indoline]-1′-yl)methyl)oxazole-4-carboxylic acid (0.41 g, 1.0 mmol), N-hydroxybenzotriazole (0.20 g, 1.5 mmol) and 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (0.29 g, 1.5 mmol) in dichloromethane (10 mL) was stirred for 30 min, followed by the addition of cyclopropylamine (0.8 mL). The solution was stirred at ambient temperature for 16 h, diluted with dichloromethane (100 mL), washed with distilled water (2×50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by flash chromatography with ethyl acetate in hexanes (gradient: 50% to 75%) to afford N-(1-methylethyl)-2-[(2′-oxospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-1′(2′H)-yl)methyl]-1,3-oxazole-4-carboxamide (0.40 g, 91%) as a colorless solid: mp 188-191° C.; 1H NMR (300 MHz, CDCl3) δ8.14 (s, 1H), 7.28-7.22 (m, 1H), 7.19 (d, J=6.8 Hz, 1H), 7.07 (dd, J=7.4, 7.4 Hz, 1H), 6.85 (d, J=7.7 Hz, 2H), 6.49 (s, 1H), 6.16 (s, 1H), 5.85 (ABq, 2H), 5.04 (ABq, 2H), 4.81 (ABq, 2H), 2.82 (m, 1H), 0.85-0.77 (m, 2H), 0.64-0.58 (m, 2H); 13C NMR (75M Hz, CDCl3) δ177.2, 161.3, 158.1, 155.8, 149.0, 142.4, 141.8, 141.0, 136.6, 132.0, 129.1, 124.15, 124.10, 119.2, 108.6, 103.0, 101.6, 93.7, 80.2, 58.2, 37.1, 22.3, 6.60, 6.55; MS (ES+) m/z 446.2 (M+1).

Workup

  1. washwashed with distilled water (2×50 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo to dryness
  5. customThe residue was purified by flash chromatography with ethyl acetate in hexanes (gradient: 50% to 75%)

Sources & evidence

ORD record
ord-5d4bb8a62a884099a965b9fb71e30472
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

Loading…