Isopropyl isocyanate → HCID 86663003, compound

HRID 1811117Notes

Reaction equation

HRID 1811117 reaction equation
NC[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(C(C)C)=C=O>C1COCC1>[CH3:35][C:20]1[C:21]([N:25]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]2=[O:34])=[CH:22][CH:23]=[CH:24][C:19]=1[C:8]1[C:7]2[C:6]3[C:14](=[CH:15][CH:3]=[CH:4][CH:5]=3)[NH:13][C:12]=2[C:11]([C:16]([NH2:18])=[O:17])=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 61277Isopropyl isocyanateHCID 59375043HCID 59375043, compound

Product 1

HCID 86663003HCID 86663003, compoundYield 20.7%

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 (1 H, d, J=7.7 Hz), 7.77 (1 H, d, J=7.5 Hz), 7.53-7.63 (2 H, m), 7.38-7.51 (4 H, m), 7.30 (1 H, dd, J=7.2, 1.7 Hz), 6.93-6.99 (2 H, m), 6.85 (1 H, dd, J=8.3, 1.4 Hz), 4.79-4.91 (2 H, m), 4.33 (2 H, s), 3.69-3.78 (1 H, m), 1.79 (3 H, s), 1.03 (6 H, 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-d77c63fd9f6f445dba700abd4c8024e7
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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