m-Chloroperbenzoic acid → HCID 178476875, compound

HRID 1948034Notes

Reaction equation

HRID 1948034 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:32]=[CH:31][C:30]([C@H:33]4[CH2:38][CH2:37][C@H:36]([OH:39])[CH2:35][CH2:34]4)=[C:29]4[C:25]=3[C:26](=[O:41])[N:27]([CH3:40])[CH2:28]4)[C:20]([C:42]([F:45])([F:44])[F:43])=[CH:19][N:18]=2)=[C:12]([O:46][CH3:47])[CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[C:48]([O:52][P:53](N(CC)CC)[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:51])([CH3:50])[CH3:49].N1C=NN=N1.C1C=C(Cl)C=C(C(OO)=[O:77])C=1>C(Cl)Cl>[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:32]=[CH:31][C:30]([C@H:33]4[CH2:34][CH2:35][C@H:36]([O:39][P:53]([O:52][C:48]([CH3:49])([CH3:50])[CH3:51])([O:54][C:55]([CH3:56])([CH3:57])[CH3:58])=[O:77])[CH2:37][CH2:38]4)=[C:29]4[C:25]=3[C:26](=[O:41])[N:27]([CH3:40])[CH2:28]4)[C:20]([C:42]([F:43])([F:44])[F:45])=[CH:19][N:18]=2)=[C:12]([O:46][CH3:47])[CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

Participants

6

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 4251849Di-tert-butyl diethylphosphoramiditeHCID 178418441HCID 178418441, compoundHCID 178476865HCID 178476865, compound

Product 1

HCID 178476875HCID 178476875, compoundYield 29.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of diethyl(4-{[4-{[7-(trans-4-hydroxycyclohexyl)-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (100.0 mg, 0.15 mmol), di(tert-butyl)N,N-diethylphosphoramidite (367.9 mg, 1.48 mmol), and 1H-tetrazole (113.7 mg, 1.62 mmol) in DCM (5 mL) was stirred at rt for 18 h. The mixture was then cooled to −78° C. and mCPBA (43.65 mg, 0.18 mmol) was added. The resulting mixture was allowed to warm to rt during 1 h, and stirred for another 14 h. The mixture was concentrated in vacuo and the residue was purified by silica gel chromatography (5% 7 N ammonia in MeOH in DCM) to afford 38.5 mg of the desired product. 1H NMR (CDCl3, 400 MHz): δ=1.27 (t, J=7.2 Hz, 6H), 1.51 (s, 18H), 1.60-1.71 (m, 4H), 1.90-1.93 (m, 2H), 2.30-2.32 (m, 2H), 2.52 (dt, J=2.4, 7.2 Hz, 1H), 3.18 (d, J=21.60 Hz, 2H), 3.22 (s, 3H), 3.93 (s, 3H), 4.00-4.09 (m, 4H), 4.38 (s, 2H), 6.88 (dt, J=2.0, 8.4 Hz, 1H), 6.95 (t, J=2.0 Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.65 (s, 1H), 8.28 (d, J=7.6 Hz, 1H), 8.39 (s, 1H), 8.64 (d, J=8.8 Hz, 1H), 10.51 (s, 1H). MS (ES+): m/z 870.39 [MH+]. HPLC: tR=4.67 min (ZQ3, polar—5 min).

Workup

  1. temperatureto warm to rt during 1 h
  2. concentrationThe mixture was concentrated in vacuo
  3. customthe residue was purified by silica gel chromatography (5% 7 N ammonia in MeOH in DCM)

Sources & evidence

ORD record
ord-07f908f25c354a6fb953d9714ebe1b4d
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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