Potassium Carbonate → 5-{2-[4-(4-Methyl-benzothiazol-2-yloxy)-phenyl]-ethyl}-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide

HRID 384532Notes

Reaction equation

HRID 384532 reaction equation
Cl.[CH2:2]1[CH:6]2[CH2:7][NH:8][CH2:9][CH:5]2[CH2:4][N:3]1[C:10]([NH2:12])=[O:11].[CH2:13]1C2CNCC2CN1C(N)=O.C([O-])([O-])=O.[K+].[K+].CS([CH2:34][CH2:35][C:36]1[CH:52]=[CH:51][C:39]([O:40][C:41]2[S:42][C:43]3[CH:49]=[C:48](C)[CH:47]=[CH:46][C:44]=3[N:45]=2)=[CH:38][CH:37]=1)(=O)=O>C(Cl)Cl.CO.C(O)(CC)(C)C>[CH3:13][C:46]1[C:44]2[N:45]=[C:41]([O:40][C:39]3[CH:38]=[CH:37][C:36]([CH2:35][CH2:34][N:8]4[CH2:7][CH:6]5[CH2:2][N:3]([C:10]([NH2:12])=[O:11])[CH2:4][CH:5]5[CH2:9]4)=[CH:52][CH:51]=3)[S:42][C:43]=2[CH:49]=[CH:48][CH:47]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 57448388Hexahydropyrrolo[3,4-c]pyrrole-2(1h)-carboxamide hydrochlorideHCID 57448389Hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amideHCID 67206214HCID 67206214, compound

Product 1

HCID 425976575-{2-[4-(4-Methyl-benzothiazol-2-yloxy)-phenyl]-ethyl}-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amideYield 5%

Reagents, catalysts & solvents 2

HCID 64052-Methyl-2-butanolSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide hydrochloride in 50% CH2Cl2/CH3OH was treated with DOWEX Monosphere 550A (OH) anion-exchange resin to afford the free base. The DOWEX resin was filtered and the resulting solution was concentrated and used without further purification. To a solution of this hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide (85 mg, 0.54 mmol) and K2CO3 (116 mg, 0.84 mmol) in tert-amyl alcohol (2.6 mL) was added 2-[4-(2-methanesulfonyl-ethyl)-phenoxy]-6-methyl-benzothiazole (120 mg, 0.34 mmol). The reaction mixture was heated to 80° C. for 16 h. The reaction mixture was filtered and washed with CH3OH. The resulting liquid was purified by preparative reverse phase HPLC to afford the title compound (11 mg, 5%). MS (ESI): mass calcd. for C23H26N4O2S, 422.55; m/z found, 423.2 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.62 (d, J=8.3 Hz, 1H), 7.48 (s, 1H), 7.28 (s, 4H), 7.20 (dd, J=8.3, 1.1 Hz, 1H), 4.39 (s, 2H), 3.60 (dd, J=10.2, 8.2 Hz, 2H), 3.30 (dd, J=10.0, 1.9 Hz, 2H), 2.98-2.87 (m, 2H), 2.86-2.80 (m, 2H), 2.76 (dd, J=9.3, 6.9 Hz, 2H), 2.74-2.67 (m, 2H), 2.53 (dd, J=9.3, 3.4 Hz, 2H), 2.45 (s, 3H).

Workup

  1. customto afford the free base
  2. filtrationThe DOWEX resin was filtered
  3. concentrationthe resulting solution was concentrated
  4. customused without further purification
  5. filtrationThe reaction mixture was filtered
  6. washwashed with CH3OH
  7. customThe resulting liquid was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-6bf6d45f4fd548579908aa21b9b3b883
Source dataset
uspto-grants-2013_02
Patent number
US08367719B2

Reaction notes

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