Sodium Carbonate → HCID 68006956, compound

HRID 526998Notes

Reaction equation

HRID 526998 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C@:11]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])([OH:15])[CH2:10]2)[C:5]([F:21])=[CH:4][N:3]=1.[Cl:22][C:23]1[CH:24]=[C:25]2[C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][N:29](S(C3C=CC(C)=CC=3)(=O)=O)[C:26]2=[N:27][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.CS(C)=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>[ClH:1].[Cl:22][C:23]1[CH:24]=[C:25]2[C:31]([C:2]3[N:7]=[C:6]([NH:8][C@H:9]4[CH2:14][CH2:13][CH2:12][C@:11]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])([OH:15])[CH2:10]4)[C:5]([F:21])=[CH:4][N:3]=3)=[CH:30][NH:29][C:26]2=[N:27][CH:28]=1

Participants

7

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 86667427HCID 86667427, compound2×

Product 1

HCID 68006956HCID 68006956, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
130 °C

Procedure

N-{[(1S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxycyclohexyl]-methyl}-acetamide, 46c, (0.2 g, 0.6 mmol) was dissolved in acetonitrile (6 mL) and treated with 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (0.5 g, 1.2 mmol) followed by Pd(PPh3)4 (0.07 g, 0.06 mmol). Aqueous 2M sodium carbonate (3.0 mL, 6.1 mmol) was added, and the vial was sealed and heated in the microwave to 130° C. for 30 min. The organic layer was collected and concentrated in vacuo to provide the crude product, which was dissolved in DMSO and purified by HPLC using 5-70% MeOH/H2O with 6 mM HCl over 15 minutes to provide after concentration 75 mg of N-{[(1S,3S)-3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-1-hydroxycyclohexyl]methyl}acetamide hydrochloride as an off-white crystalline solid.

Workup

  1. customthe vial was sealed
  2. customThe organic layer was collected
  3. concentrationconcentrated in vacuo
  4. customto provide the crude product, which
  5. custompurified by HPLC
  6. customover 15 minutes

Sources & evidence

ORD record
ord-01343cdb79894fec9b1708f42a939e56
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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