Isopropyl isocyanate → HCID 59375071, compound

HRID 661936Notes

Reaction equation

HRID 661936 reaction equation
[NH2:1][CH2:2][C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[CH2:33][C:32]6[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=6)[C:26]5=[O:34])[C:20]=4[CH3:35])=[CH:9][CH:10]=[C:11]([C:16]([NH2:18])=[O:17])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1.[N:36]([CH:39]([CH3:41])[CH3:40])=[C:37]=[O:38]>C1COCC1>[CH:39]([NH:36][C:37](=[O:38])[NH:1][CH2:2][C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[CH2:33][C:32]6[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=6)[C:26]5=[O:34])[C:20]=4[CH3:35])=[CH:9][CH:10]=[C:11]([C:16]([NH2:18])=[O:17])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1)([CH3:41])[CH3:40]

Participants

4

Reactant 2

HCID 61277Isopropyl isocyanateHCID 59375043HCID 59375043, compound

Product 1

HCID 59375071HCID 59375071, compoundYield 16.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 7-(aminomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 33-1, 30 mg, 0.065 mmol) and 2-isocyanatopropane (0.019 mL, 0.195 mmol) in THF (3 mL) was stirred at 40° C. overnight. The mixture was concentrated and purified by preparative HPLC. The appropriate effluent fractions were concentrated and partitioned between EtOAc and NaHCO3 (aq). The organic phase was dried and concentrated to provide 7-((3-isopropylureido)methyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide as a white solid (5.8 mg, 14%). 1H NMR (400 MHz, methanol-d4) δ 7.84 (1H, d, J=7.7 Hz), 7.77 (1H, d, J=7.5 Hz), 7.53-7.63 (2H, m), 7.38-7.51 (4 H, m), 7.30 (1H, dd, J=7.2, 1.7 Hz), 6.93-6.99 (2H, m), 6.85 (1H, dd, J=8.3, 1.4 Hz), 4.79-4.91 (2H, m), 4.33 (2H, s), 3.69-3.78 (1H, m), 1.79 (3H, s), 1.03 (6H, d, J=6.4 Hz). Mass spectrum m/z 546.3 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC
  3. concentrationThe appropriate effluent fractions were concentrated
  4. custompartitioned between EtOAc and NaHCO3 (aq)
  5. customThe organic phase was dried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-25e02c6758134f2d950d208c151d2c00
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

Loading…