1,4-Dioxane → HCID 59605558, compound

HRID 1945751Notes

Reaction equation

HRID 1945751 reaction equation
[CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([Sn](CCCC)(CCCC)CCCC)=[N:6][C:7]=2[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.[C:41]1([S:47]([N:50]2[C:54]3=[CH:55][N:56]=[CH:57][C:58](Br)=[C:53]3[CH:52]=[CH:51]2)(=[O:49])=[O:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.O1CCOC[CH2:61]1>C1C=C(C([O-])=O)SC=1.[Cu+].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>[C:41]1([S:47]([N:50]2[C:54]3=[CH:55][N:56]=[CH:57][C:58]([C:5]4[N:4]=[C:3]5[C:8]([N:9]=[C:10]([CH2:11][N:12]6[CH2:13][CH2:14][CH:15]([C:18]([OH:21])([CH3:19])[CH3:20])[CH2:16][CH2:17]6)[N:2]5[CH3:1])=[C:7]([N:22]5[CH2:23][CH2:24][O:25][CH2:26][CH2:27]5)[N:6]=4)=[C:53]3[CH:52]=[C:51]2[CH3:61])(=[O:49])=[O:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 583564464-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridineHCID 596055362-(1-((9-Methyl-6-morpholino-2-(tributylstannyl)-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

Product 1

HCID 59605558HCID 59605558, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
150 °C

Procedure

A 20 mL microwave vial was charged with a suspension of 2-[1-(9-methyl-6-morpholin-4-yl-2-(tributylstannanyl)-9H-purin-8-ylmethyl)piperidin-4-yl]propan-2-ol (0.5 g, 0.75 mmol), 1-benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-c]pyridine (0.29 g, 0.83 mmol), CuTC (0.029 g, 0.015 mmol) and Pd(PPh3)4 (0.087 g, 0.075 mmol) in dioxane (8 mL). The reaction mixture was heated in a microwave for 30 min at 150° C. The cooled reaction mixture was loaded onto an SCX-2 cartridge. The cartridge was washed with 3 volumes of MeOH, then the product was recovered eluting with 2N ammonia in MeOH. The solution was concentrated and the residue loaded onto a 40 g SiO2 column and purified by flash chromatography (Si—PCC; 40 g SiO2 column, 0% to 6% MeOH in DCM) to give 2-{1-[2-(1-Benzenesulfonyl-2-methyl-1H-pyrrolo[2,3-c]pyridin-4-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl]piperidin-4-yl}propan-2-ol as white foam (0.414 g, 86%). LCMS (Method A): RT=3.24 min, [M+H]+ 645.3

Workup

  1. customThe cooled reaction mixture
  2. washThe cartridge was washed with 3 volumes of MeOH
  3. customthe product was recovered
  4. washeluting with 2N ammonia in MeOH
  5. concentrationThe solution was concentrated
  6. custompurified by flash chromatography (Si—PCC; 40 g SiO2 column, 0% to 6% MeOH in DCM)

Sources & evidence

ORD record
ord-c3d02ac0cc39465fbbd3a40608ad0ef2
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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