1,2-Dimethoxyethane → HCID 71240482, compound

HRID 80808Notes

Reaction equation

HRID 80808 reaction equation
COCCOC.[CH2:7]([N:14]1[CH2:43][CH2:42][C:17]2[N:18]=[C:19](Cl)[N:20]=[C:21]([N:22]3[CH2:27][CH2:26][N:25]([S:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[N+:37]([O-:39])=[O:38])(=[O:30])=[O:29])[C@H:24]([CH3:40])[CH2:23]3)[C:16]=2[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH3:44][C:45]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][C:52]=2B2OC(C)(C)C(C)(C)O2)[N:47]([S:63]([C:66]2[CH:72]=[CH:71][C:69]([CH3:70])=[CH:68][CH:67]=2)(=[O:65])=[O:64])[CH:46]=1.C([O-])([O-])=O.[Na+].[Na+]>CCOCC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:7]([N:14]1[CH2:43][CH2:42][C:17]2[N:18]=[C:19]([C:52]3[CH:51]=[CH:50][CH:49]=[C:48]4[C:53]=3[C:45]([CH3:44])=[CH:46][N:47]4[S:63]([C:66]3[CH:72]=[CH:71][C:69]([CH3:70])=[CH:68][CH:67]=3)(=[O:65])=[O:64])[N:20]=[C:21]([N:22]3[CH2:27][CH2:26][N:25]([S:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[N+:37]([O-:39])=[O:38])(=[O:30])=[O:29])[C@H:24]([CH3:40])[CH2:23]3)[C:16]=2[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 712404273-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indoleHCID 86690263(R)-6-benzyl-2-chloro-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 71240482HCID 71240482, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
140 °C

Procedure

1,2-Dimethoxyethane (6.75 mL) was added to a 20 mL microwave vial containing a mixture of (R)-6-benzyl-2-chloro-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (1.1 g, 2.03 mmol) and 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole (0.92 g, 2.23 mmol). Then 2M aqueous Na2CO3 was added and the reaction mixture was degassed via three argon/vacuum cycles, then charged with Pd(Ph3P)4 (0.234 g, 0.203 mmol). The vial was sealed and heated via microwave irradiation at 140° C. for 90 minutes. The mixture was then cooled to room temperature and diluted with Et2O and water. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic layers were combined dried over MgSO4, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography [55-75% ethyl acetate (containing 2% EtOH)/heptanes] to afford (R)-6-benzyl-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. MS (ESI+) m/z 792.5 (M+H)+.

Workup

  1. additioncontaining
  2. customthe reaction mixture was degassed via three argon/vacuum cycles
  3. customThe vial was sealed
  4. temperatureThe mixture was then cooled to room temperature
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted two additional times with dichloromethane
  7. dry with materialThe organic layers were combined dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel flash chromatography [55-75% ethyl acetate (containing 2% EtOH)/heptanes]

Sources & evidence

ORD record
ord-c9a0af297da54cc8890daf0de8cb7dd4
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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