1,4-Dioxane → (2R,6S,13aR,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-5,16-dioxo-2-(3-phenylquinoxalin-2-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate

HRID 1966489Notes

Reaction equation

HRID 1966489 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]3[C:38](Cl)=[N:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)[CH2:27][C@H:21]2[C:20](=[O:40])[NH:19][C@:18]2([C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:41][C@@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Sn](CCCC)(CCCC)C1S[C:54]2[CH:60]=[CH:59][CH:58]=[CH:57][C:55]=2N=1)CCC.O1CCOCC1>CC#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]3[C:38]([C:54]4[CH:60]=[CH:59][CH:58]=[CH:57][CH:55]=4)=[N:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)[CH2:27][C@H:21]2[C:20](=[O:40])[NH:19][C@:18]2([C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:41][C@@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 37623922-(Tributylstannyl)-1,3-benzothiazoleHCID 25010469(2R,6S,13aR,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-(3-chloroquinoxalin-2-yloxy)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate

Product 1

HCID 68500607(2R,6S,13aR,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-5,16-dioxo-2-(3-phenylquinoxalin-2-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylateYield 92.7%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6342AcetonitrileSolvent

Procedure

To a microwave vessel was added the product from 1b (700 mg. 1.07 mmole), 2-(tributylstannyl)benzo[d]thiazole (905 mg, 2.13 mmole), palladium-tetrakis(triphenylphosphine) (113 mg, 0.11 mmole) and dioxane (5 ml). The vessel was evacuated and nitrogen introduced, which was repeated twice. The mixture was reacted in a microwave reactor at 110 degrees C. for 1 hr. The reaction was diluted with MeCN and washed 3 times with hexane. The MeCN layer was evaporated and purified by column chromatography on silica gel (CHCl3-EtOAc gradient) to obtain the title compound (692 mg, 86% yield). MS(ESI): m/z=755.2 [M+H].

Workup

  1. customThe vessel was evacuated
  2. additionnitrogen introduced
  3. customThe mixture was reacted in a microwave reactor at 110 degrees C
  4. washwashed 3 times with hexane
  5. customThe MeCN layer was evaporated
  6. custompurified by column chromatography on silica gel (CHCl3-EtOAc gradient)

Sources & evidence

ORD record
ord-d35b3cdef63240f8b7994074dcac8af1
Source dataset
uspto-grants-2013_04
Patent number
US08420596B2

Reaction notes

Loading…