Sodium Carbonate → HCID 68007943, compound

HRID 527045Notes

Reaction equation

HRID 527045 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.Cl[C:31]1[N:36]=[C:35]([NH:37][C@H:38]2[CH2:43][CH2:42][CH2:41][C@@:40]([CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])([OH:44])[CH2:39]2)[C:34]([F:51])=[CH:33][N:32]=1.C([O-])([O-])=O.[Na+].[Na+]>C(#N)C.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>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:31]3[N:36]=[C:35]([NH:37][C@H:38]4[CH2:43][CH2:42][CH2:41][C@@:40]([CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])([OH:44])[CH2:39]4)[C:34]([F:51])=[CH:33][N:32]=3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 575977475-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 86719750HCID 86719750, compound2×

Product 1

HCID 68007943HCID 68007943, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (0.31 g, 0.72 mmol) in acetonitrile (6.0 mL) was added ethyl 2-((1R,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxy-cyclohexyl)ethanoate, 60a, (0.20 g, 0.60 mmol) and degassed under N2. Na2CO3 (0.90 mL of 2 M, 1.81 mmol) was added followed by Pd(PPh3)4 (0.10 g, 0.09 mmol). The reaction was sealed and microwaved at 120° C. for 30 min. The material was concentrated under reduced pressure then diluted in EtOAc and aqueous saturated NaHCO3, then extracted with additional EtOAc (3×), dried (Na2SO4) and concentrated in vacuo. The material was diluted in DCM and silica gel chromatography (Hexanes:EtOAc) gave 217 mg of product 60c. LC MS+: 602.49 at 4.62 min (10-90% MeOH, 3/5 grad/run, Formic Acid).

Workup

  1. customdegassed under N2
  2. customThe reaction was sealed
  3. custommicrowaved at 120° C. for 30 min
  4. concentrationThe material was concentrated under reduced pressure
  5. additionthen diluted in EtOAc
  6. extractionaqueous saturated NaHCO3, then extracted with additional EtOAc (3×)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. additionThe material was diluted in DCM

Sources & evidence

ORD record
ord-30ec2282004946c495d4595ece2c9e95
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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