Tetrabutylammonium Fluoride → HCID 59375124, compound

HRID 1811149Notes

Reaction equation

HRID 1811149 reaction equation
[Si]([O:8][C:9]1([C:12]2[CH:24]=[C:23]3[C:15]([C:16]4[C:17]([C:28]5[CH:33]=[CH:32][CH:31]=[C:30]([N:34]6[CH2:42][C:41]7[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=7)[C:35]6=[O:43])[C:29]=5[CH3:44])=[CH:18][CH:19]=[C:20]([C:25]([NH2:27])=[O:26])[C:21]=4[NH:22]3)=[CH:14][CH:13]=2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[OH:8][C:9]1([C:12]2[CH:24]=[C:23]3[C:15]([C:16]4[C:17]([C:28]5[CH:33]=[CH:32][CH:31]=[C:30]([N:34]6[CH2:42][C:41]7[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=7)[C:35]6=[O:43])[C:29]=5[CH3:44])=[CH:18][CH:19]=[C:20]([C:25]([NH2:27])=[O:26])[C:21]=4[NH:22]3)=[CH:14][CH:13]=2)[CH2:10][CH2:11]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 66606338HCID 66606338, compound

Product 1

HCID 59375124HCID 59375124, compoundYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Step 4 A solution of 7-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (0.039 g, 0.065 mmol) in THF (0.66 mL) was treated with tetra-n-butylammonium fluoride (1 M in THF, 0.098 mL, 0.098 mmol). After 10 min, the mixture was combined with an identical reaction mixture done on 22% of the scale described, and the mixture was concentrated. The residue was purified by preparative HPLC. The appropriate effluent fractions were treated with NaHCO3 (aq) and partially concentrated. The aqueous residue was extracted three times with DCM and the combined organic phases were dried and concentrated to give 7-(1-hydroxycyclopropyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide as a white solid (23.3 mg, 60%). 1H NMR (500 MHz, DMSO-d6) δ 11.42 (1 H, s), 8.18 (1 H, br. s.), 7.98 (1 H, d, J=7.7 Hz), 7.80 (1 H, d, J=7.7 Hz), 7.72 (1 H, s), 7.68 (2 H, d, J=3.8 Hz), 7.60 (1H, d, J=7.7 Hz), 7.56 (1 H, ddd, J=7.8, 4.1, 4.0 Hz), 7.49 (2 H, t, J=7.7 Hz), 7.33 (1H, d, J=7.1 Hz), 7.01 (1 H, d, J=7.7 Hz), 6.95 (1 H, d, J=8.2 Hz), 6.79 (1 H, d, J=8.2 Hz), 5.95 (1 H, s), 4.90-5.02 (2 H, m), 1.84 (3 H, s), 1.07-1.15 (2 H, m), 0.91-1.00 (2 H, m). Mass spectrum m/z 488.3 (M+H)+.

Workup

  1. concentrationthe mixture was concentrated
  2. customThe residue was purified by preparative HPLC
  3. additionThe appropriate effluent fractions were treated with NaHCO3 (aq)
  4. concentrationpartially concentrated
  5. extractionThe aqueous residue was extracted three times with DCM
  6. customthe combined organic phases were dried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-11133d2caa394caf8f27f61f425b622a
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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