Sodium Carbonate → HCID 71283206, compound

HRID 1752447Notes

Reaction equation

HRID 1752447 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[CH:16]=[CH:15][C:14](B4OC(C)(C)C(C)(C)O4)=[CH:13][CH:12]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.[NH2:26][C:27](=[O:41])[C@@H:28]([NH:30][C:31]1[N:36]=[C:35](Cl)[N:34]=[C:33]([C:38]([NH2:40])=[O:39])[CH:32]=1)[CH3:29].C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[NH2:26][C:27](=[O:41])[CH:28]([NH:30][C:31]1[N:36]=[C:35]([C:14]2[CH:13]=[CH:12][C:11]([O:10][C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)=[CH:16][CH:15]=2)[N:34]=[C:33]([C:38]([NH2:40])=[O:39])[CH:32]=1)[CH3:29].[NH2:26][C:27](=[O:41])[C@@H:28]([NH:30][C:31]1[N:36]=[C:35]([C:14]2[CH:13]=[CH:12][C:11]([O:10][C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)=[CH:16][CH:15]=2)[N:34]=[C:33]([C:38]([NH2:40])=[O:39])[CH:32]=1)[CH3:29]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 712856355-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]-1,3-benzodioxoleHCID 89422280HCID 89422280, compound

Product 2

HCID 71283206HCID 71283206, compoundYield 87.2%HCID 71283211HCID 71283211, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 50-mL vial with a screw-top septum was charged with 200 mg of 2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 1 equivalent of (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-chloropyrimidine-4-carboxamide (1.53 mg, 0.59 mmol), 1.5 mL 2M aqueous Na2CO3, 0.07 equivalents of PdCl2(PPh3)2 (28 mg, 0.04 mmol), and 8 mL dioxane. The vial was purged with nitrogen and heated to 100° C. for 6 h, at which time the reaction was complete. The mixture was diluted with 100 mL EtOAc and washed two times with 100 mL water. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was chromatographed by combiflash using a 40-gram silica column with a gradient EtOAc (100% max) in hexane to provide 108 mg (43% yield) of S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)pyrimidine-4-carboxamide as a white solid. m/z 421, 1H NMR (CD3OD): 8.51-8.41 (m, 2H), 7.14-7.07 (s, 1H), 7.01-6.93 (m, 2H), 6.86-6.78 (m, 1H), 6.64-6.60 (m, 1H), 6.57-6.50 (m, 1H), 6.01-5.95 (s, 2H), 4.61-4.49 (m, 1H), 1.56-1.48 (m, 3H).

Workup

  1. customThe vial was purged with nitrogen
  2. additionThe mixture was diluted with 100 mL EtOAc
  3. washwashed two times with 100 mL water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was chromatographed by combiflash

Sources & evidence

ORD record
ord-d35380ee3fdb4cca9664f83241fb106a
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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