Dimethyl Sulfoxide → HCID 56591344, compound

HRID 1035911Notes

Reaction equation

HRID 1035911 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([O:10][C:11]3[CH:32]=[C:31]([N:33]4[CH2:38][CH2:37][N:36]([CH2:39][C:40]5[CH2:45][CH2:44][C:43]([CH3:47])([CH3:46])[CH2:42][C:41]=5[C:48]5[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][CH:49]=5)[CH2:35][CH2:34]4)[CH:30]=[CH:29][C:12]=3[C:13]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][C:22](Cl)=[C:21]([N+:26]([O-:28])=[O:27])[CH:20]=3)(=[O:18])=[O:17])=[O:14])[CH:9]=[C:4]2[CH:3]=[CH:2]1.[O:55]1[CH2:60][CH2:59][CH:58]([N:61]2[CH2:64][CH:63]([NH2:65])[CH2:62]2)[CH2:57][CH2:56]1.C(N(CC)CC)C.CS(C)=O>O1CCOCC1.O>[Cl:54][C:51]1[CH:52]=[CH:53][C:48]([C:41]2[CH2:42][C:43]([CH3:47])([CH3:46])[CH2:44][CH2:45][C:40]=2[CH2:39][N:36]2[CH2:37][CH2:38][N:33]([C:31]3[CH:30]=[CH:29][C:12]([C:13]([NH:15][S:16]([C:19]4[CH:24]=[CH:23][C:22]([NH:65][CH:63]5[CH2:62][N:61]([CH:58]6[CH2:59][CH2:60][O:55][CH2:56][CH2:57]6)[CH2:64]5)=[C:21]([N+:26]([O-:28])=[O:27])[CH:20]=4)(=[O:17])=[O:18])=[O:14])=[C:11]([O:10][C:8]4[CH:9]=[C:4]5[CH:3]=[CH:2][NH:1][C:5]5=[N:6][CH:7]=4)[CH:32]=3)[CH2:34][CH2:35]2)=[CH:49][CH:50]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471Triethylamine2×HCID 56591275HCID 56591275, compoundHCID 63937892HCID 63937892, compound

Product 1

HCID 56591344HCID 56591344, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-N-(4-chloro-3-nitrophenylsulfonyl)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)benzamide (0.180 g), 1-(tetrahydro-2H-pyran-4-yl)azetidin-3-amine (0.078 g), and triethylamine (0.159 mL) in dioxane (2 mL) was degassed with nitrogen for 30 seconds then sealed. The reaction was heated to 110° C. After stirring for 16 hours, more triethylamine (10 equivalents total) and dimethylsulfoxide (1 mL) were added and the reaction stirred for an additional 18 hours at 110° C. The reaction was cooled, diluted with water (50 mL) and extracted with dichloromethane (2×150 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (GraceResolv 12 g) eluting with a gradient of 0.75% to 7.5% methanol/dichloromethane (Flow=36 mL/minutes) gave the title compound. 1H NMR (300 MHz, dimethylsulfoxide-d6) δ 11.59 (s, 1H), 8.49 (d, 1H), 8.40 (s, 1H), 7.97 (d, 1H), 7.77 (s, 1H), 7.47 (dd, 3H), 7.34 (d, 2H), 7.04 (d, 2H), 6.90-6.78 (m, 1H), 6.65 (d, 1H), 6.35 (s, 1H), 6.21 (s, 1H), 4.47-4.23 (m, 1H), 3.83 (s, 3H), 3.05 (s, 6H), 2.73 (s, 2H), 2.18 (s, 8H), 1.95 (s, 2H), 1.68 (s, 2H), 1.38 (s, 2H), 1.24 (s, 4H), 0.92 (s, 6H).

Workup

  1. customwas degassed with nitrogen for 30 seconds
  2. customthen sealed
  3. stirringthe reaction stirred for an additional 18 hours at 110° C
  4. temperatureThe reaction was cooled
  5. extractionextracted with dichloromethane (2×150 mL)
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washSilica gel chromatography (GraceResolv 12 g) eluting with a gradient of 0.75% to 7.5% methanol/dichloromethane (Flow=36 mL/minutes)

Sources & evidence

ORD record
ord-2bc920bcc3b14c7c89c2cee96455293e
Source dataset
uspto-grants-2013_10
Patent number
US08546399B2

Reaction notes

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