1,2-Dichloroethane → HCID 59375067, compound

HRID 1811116Notes

Reaction equation

HRID 1811116 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.[C:36](O)(=[O:39])[CH2:37][OH:38].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>C(#N)C.C1COCC1>[OH:39][CH2:36][C:37]([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)=[O:38]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 757Glycolic AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 59375043HCID 59375043, compound

Product 1

HCID 59375067HCID 59375067, compoundYield 60.7%

Reagents, catalysts & solvents 1

HCID 22177404Acetonitrile tetrahydrofuranSolvent

Procedure

A solution of crude 7-(aminomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 33-1, 25 mg, 0.054 mmol), glycolic acid (8.26 mg, 0.109 mmol), HOAT (13.30 mg, 0.098 mmol), and EDC (20.81 mg, 0.109 mmol) in acetonitrile-THF (2:1) (5 mL) was treated with DIEA (0.028 mL, 0.163 mmol) and stirred at rt overnight. The mixture was concentrated and purified by preparative HPLC. The appropriate effluent fractions were concentrated to afford an aqueous suspension, which was treated with NaHCO3 (aq). The precipitate was collected by filtration, washed with water and dried to provide 7-((2-hydroxyacetamido)methyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (17 mg, 59%). 1H NMR (400 MHz, DMSO-d6) δ 11.49 (1H, s), 8.22-8.28 (1 H, m), 8.17 (1 H, br. s.), 7.97-8.05 (1 H, m), 7.81 (1 H, d, J=7.5 Hz), 7.69 (2 H, d, J=3.7 Hz), 7.54-7.66 (3 H, m), 7.42-7.54 (2 H, m), 7.28-7.38 (1H, m), 7.03 (1 H, d, J=7.9 Hz), 6.94-7.00 (1 H, m), 6.86-6.94 (1 H, m), 5.45 (1 H, br.), 4.88-5.05 (2 H, m), 4.33-4.48 (2 H, m), 3.88 (2 H, s), 1.83 (3 H, s). Mass spectrum m/z 519.2 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC
  3. concentrationThe appropriate effluent fractions were concentrated
  4. customto afford an aqueous suspension, which
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with water
  7. customdried

Sources & evidence

ORD record
ord-513904fc59c840b7adf658ceb5f30933
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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