TBAF tetrahydrofuran → HCID 67995186, compound

HRID 2361318Notes

Reaction equation

HRID 2361318 reaction equation
[Si]([O:8][CH:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]4[C:26]([C:27]5[CH:32]=[CH:31][CH:30]=[C:29]([N:33]6[CH2:41][C:40]7[C:35](=[CH:36][C:37]([Cl:42])=[CH:38][CH:39]=7)[C:34]6=[O:43])[C:28]=5[CH3:44])=[CH:25][N:24]=[C:23]([C:45]([NH2:47])=[O:46])[C:19]=4[NH:20]3)=[CH:16][CH:15]=2)[CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>O1CCCC1>[Cl:42][C:37]1[CH:36]=[C:35]2[C:40]([CH2:41][N:33]([C:29]3[C:28]([CH3:44])=[C:27]([C:26]4[C:18]5[C:17]6[C:21](=[CH:22][C:14]([N:11]7[CH2:12][CH2:13][CH:9]([OH:8])[CH2:10]7)=[CH:15][CH:16]=6)[NH:20][C:19]=5[C:23]([C:45]([NH2:47])=[O:46])=[N:24][CH:25]=4)[CH:32]=[CH:31][CH:30]=3)[C:34]2=[O:43])=[CH:39][CH:38]=1

Participants

4

Reactant 2

HCID 11078149TBAF tetrahydrofuranHCID 67995228HCID 67995228, compound

Product 1

HCID 67995186HCID 67995186, compoundYield 29.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a homogeneous, orange solution of 7-(3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-4-(3-(6-chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (0.0456 g, 0.068 mmol) in tetrahydrofuran (0.684 mL) under nitrogen was added 1 M TBAF/THF (0.103 mL, 0.103 mmol). The reaction was stirred for 75 min and concentrated in vacuo. The residue was dissolved in DMSO (0.2 mL) and MeOH, and subjected to autoprep HPLC. The appropriate fractions were collected, basified with NaHCO3 (solid), and concentrated in vacuo. The residue was extracted with CH2Cl2 (3×). The combined extract was dried over Na2SO4 and concentrated in vacuo to give the desired product (0.0112 g, 0.020 mmol, 29.7% yield) as a light yellow solid. LC/MS (M+H)=552.11; 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for major atropoisomer) δ ppm 11.26 (s, 1H), 8.21 (d, J=2.8 Hz, 1H), 8.08 (s, 1H), 7.81 (s, 1H), 7.74 (d, J=1.94 Hz, 2H), 7.63-0.65 (m, 2H), 7.45-7.58 (m, 1H), 7.42 (d, J=1.11 Hz, 1H), 7.03 (d, J=8.60 Hz, 1H), 6.83 (d, J=1.66 Hz, 1H), 6.38 (dd, J1=9.0 Hz, J2=2.1 Hz, 1H), 5.02 (d, J=17.76 Hz, 1H), 4.95-4.98 (m, 1H), 4.94 (d, J=17.76 Hz, 1H), 4.43 (br. S, 1H), 3.47 (ddd, J1=10.2 Hz, J2=4.8 Hz, J3=2.2 Hz, 1H), 3.37-3.44 (m, 1H), 3.31-3.37 (m, 1H), 3.15 (d, J=10.0 Hz, 1H), 2.07 (dd, J=8.25, 4.30 Hz, 1H), 1.90-1.96 (m, 1H), 1.88 (s, 3H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in DMSO (0.2 mL)
  3. customThe appropriate fractions were collected
  4. concentrationconcentrated in vacuo
  5. extractionThe residue was extracted with CH2Cl2 (3×)
  6. extractionThe combined extract
  7. dry with materialwas dried over Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-613a835233d04c97b30eccc78cb87b4c
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

Loading…