Thioglycolic Acid → (3R*,5S*)-3-{Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-5-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1698368Notes

Reaction equation

HRID 1698368 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([N:14]([CH2:27][CH2:28][N:29]2[C:37](=[O:38])[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30]2=[O:39])S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[CH2:11][C@@H:10]([C:40](=[O:60])[N:41]([CH:57]2[CH2:59][CH2:58]2)[CH2:42][C:43]2[C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[N:45]([CH2:52][CH2:53][CH2:54][O:55][CH3:56])[CH:44]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)CS.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([NH:14][CH2:27][CH2:28][N:29]2[C:37](=[O:38])[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30]2=[O:39])[CH2:11][C@@H:10]([C:40](=[O:60])[N:41]([CH:57]2[CH2:59][CH2:58]2)[CH2:42][C:43]2[C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[N:45]([CH2:52][CH2:53][CH2:54][O:55][CH3:56])[CH:44]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 1133Thioglycolic AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 69071084(3R*,5S*)-3-{Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-5-[[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-(2-nitro-benzenesulfonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69066246(3R*,5S*)-3-{Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-5-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethylamino]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3R*,5S*)-3-{Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-5-[[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-(2-nitro-benzenesulfonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (250 mg, 0.3 mmol) in DMF (1 mL) are added thioglycolic acid (104 uL, 1.5 mmol) and DBU (224 uL, 1.5 mmol) at room temperature. After 2.5 h, the reaction mixture is quenched by H2O (20 mL) and extracted with CH2Cl2 (50 mL). The organic phase is successively washed with H2O and brine, then dried over Na2SO4 and concentrated in reduced pressure. The residue is purified by silica gel column chromatography to afford the title compound. MS: 658 [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 3.60 min.

Workup

  1. customthe reaction mixture is quenched by H2O (20 mL)
  2. extractionextracted with CH2Cl2 (50 mL)
  3. washThe organic phase is successively washed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in reduced pressure
  6. customThe residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-748b36c3fa0342faa882a5c2d1af10f9
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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