Ethyl Acetate → (S)-4-(2-(2-(6-amino-1-oxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

HRID 571179Notes

Reaction equation

HRID 571179 reaction equation
C(OC([NH:8][C:9]1[CH:17]=[C:16]2[C:12]([CH2:13][N:14]([CH2:19][C:20]([O:22][C@H:23]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:43])[F:42])=[C:36]([O:44][CH2:45][CH:46]4[CH2:48][CH2:47]4)[CH:35]=3)[CH2:24][C:25]3[C:30]([Cl:31])=[CH:29][N+:28]([O-:32])=[CH:27][C:26]=3[Cl:33])=[O:21])[C:15]2=[O:18])=[CH:11][CH:10]=1)=O)(C)(C)C.C(OCC)(=O)C>Cl>[NH2:8][C:9]1[CH:17]=[C:16]2[C:12]([CH2:13][N:14]([CH2:19][C:20]([O:22][C@H:23]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:42])[F:43])=[C:36]([O:44][CH2:45][CH:46]4[CH2:47][CH2:48]4)[CH:35]=3)[CH2:24][C:25]3[C:26]([Cl:33])=[CH:27][N+:28]([O-:32])=[CH:29][C:30]=3[Cl:31])=[O:21])[C:15]2=[O:18])=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 8857Ethyl AcetateHCID 86681601HCID 86681601, compound

Product 1

HCID 86681602(S)-4-(2-(2-(6-amino-1-oxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxideYield 100%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

(S)-4-(2-(2-(6-(tert-butoxycarbonylamino)-1-oxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (70 mg, 0.099 mmol) was dissolved in HCl 4M in ethyl acetate (1.5 ml, 49.4 mmol). The reaction was stirred at RT for 2 hours. The reaction mixture was concentrated under vacuum, the crude product was triturated with Et2O and filtered to give (S)-4-(2-(2-(6-amino-1-oxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (60 mg, 0.099 mmol, quantitative yield). 1H NMR (400 MHz, acetone) δ ppm 8.33 (s, 2H), 7.68-7.94 (m, 3H), 7.16-7.32 (m, 2H), 7.06 (dd, J=8.19, 1.83 Hz, 1H), 6.93 (t, 1H, CHF2), 6.12-6.23 (m, 1H), 4.61 (s, 2H), 4.46 (d, J=3.18 Hz, 2H), 3.99 (dd, J=6.85, 1.22 Hz, 2H), 3.57 (d, J=9.78 Hz, 1H), 3.37 (d, J=4.65 Hz, 1H), 1.22-1.37 (m, 1H), 0.54-0.68 (m, 2H), 0.40 (d, J=4.65 Hz, 2H); MS/ESI+ 608.42 [MH]+.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe crude product was triturated with Et2O
  3. filtrationfiltered

Sources & evidence

ORD record
ord-cf0e94068bef4b7d873b225ea51e5e77
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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