1,2-Dichloroethane → HCID 86761384, compound

HRID 1669455Notes

Reaction equation

HRID 1669455 reaction equation
[NH2:1][S:2]([N:5]([CH3:43])[CH2:6][CH2:7][N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH2:13][O:14][C@H:15]1[CH2:22][N:21]2[C:23]3[CH:24]=[C:25]([C:36](O)=[O:37])[CH:26]=[CH:27][C:28]=3[C:29]([CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)=[C:20]2[C:19]2[CH:39]=[CH:40][CH:41]=[CH:42][C:18]=2[O:17][CH2:16]1)(=[O:4])=[O:3].C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C.CS(C)=O>[CH:30]1([C:29]2[C:28]3[C:23]4=[CH:24][C:25](=[CH:26][CH:27]=3)[C:36](=[O:37])[NH:1][S:2](=[O:3])(=[O:4])[N:5]([CH3:43])[CH2:6][CH2:7][N:8]3[CH:9]([CH2:10][CH2:11][CH2:12]3)[CH2:13][O:14][C@H:15]3[CH2:22][N:21]4[C:20]=2[C:19]2[C:18]([O:17][CH2:16]3)=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1

Participants

6

Reactant 2

HCID 111,2-DichloroethaneHCID 67346915HCID 67346915, compound

Product 1

HCID 86761384HCID 86761384, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution (7 mM) of (7S)-7-[(1-{2-[(aminosulfonyl)(methyl)amino]ethyl}pyrrolidin-2-yl)methoxy]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acid in DCM, DMAP (5 eq) and EDC (2 eq) were added and the resulting mixture heated at 40° C. for 2 h and then at RT over night. Volatiles were eliminated in vacuo and the residue redissolved in DMSO. Purification was by RP-HPLC (stationary phase: column Waters XTERRA prep. C18, 5 um, 19×100 mm) eluting with MeCN/TFA buffered with 0.1% TFA gradient. Fractions containing the product were combined and freeze dried to afford the product as a white powder (34%) as a mixture of isomers. 1H NMR (600 MHz, DMSO-d6+TFA, 320 K) δ 1.15-2.02 (m, 14H), 2.68-2.70 (m, 1H), 2.94-3.08 (m, 3H), 3.14-4.11 (m, 1H), 4.32-4.61 (m, 2H), 4.81-4.90 (m, 1H), 7.16-7.39 (m, 2H), 7.40-7.49 (m, 1H), 7.50-7.57 (m, 2H), 7.85-7.94 (m, 1H), 8.13-8.43 (m, 1H); (ES+) m/z 593 (M+H)+.

Workup

  1. waitat RT over night
  2. customPurification
  3. washeluting with MeCN/TFA
  4. additionFractions containing the product
  5. customfreeze dried

Sources & evidence

ORD record
ord-2a0bce7d7650413aaf79154c578d1bd6
Source dataset
uspto-grants-2011_08
Patent number
US07989438B2

Reaction notes

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