Sodium Carbonate → HCID 44225401, compound

HRID 880522Notes

Reaction equation

HRID 880522 reaction equation
I[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:3]=1.[CH3:18][NH:19][C:20]([NH:22][C:23]1[S:24][C:25]2[CH:31]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:29]=[CH:28][C:26]=2[N:27]=1)=[O:21].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[NH2:11][C:9]1[C:10]2[C:2]([C:30]3[CH:29]=[CH:28][C:26]4[N:27]=[C:23]([NH:22][C:20]([NH:19][CH3:18])=[O:21])[S:24][C:25]=4[CH:31]=3)=[CH:3][N:4]([CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[C:5]=2[N:6]=[CH:7][N:8]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58279572HCID 58279572, compoundHCID 58279592HCID 58279592, compound

Product 1

HCID 44225401HCID 44225401, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 5-iodo-7-(tetrahydro-2H-pyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (402) (100 mg, 0.29 mmol), 1-methyl-3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)urea (J-2) (127 mg, 1.3 eq, 0.38 mmol), Pd(PPh3)4 (38 mg, 0.1 eq, 0.03 mmol) and Na2CO3 (2 N, 2 mL) in DME (10 mL) was stirred at reflux for 30 min. under argon. The mixture was cooled to room temperature, and then concentrated in vacuo. Brine (10 mL) was added to the residue and then extracted with ethyl acetate (3×30 mL). The combined organic layer was washed with brine (10 mL), dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography eluting with MeOH/DCM (1/30) to afford the desired product, 1-(6-(4-amino-7-(tetrahydro-2H-pyran-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)benzo[d]thiazol-2-yl)-3-methylurea (403) (60 mg 58% yield) as a white solid. ESI-MS m/z: 424.05 [M+H]+.

Workup

  1. temperatureat reflux for 30 min. under argon
  2. concentrationconcentrated in vacuo
  3. additionBrine (10 mL) was added to the residue
  4. extractionextracted with ethyl acetate (3×30 mL)
  5. washThe combined organic layer was washed with brine (10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by flash column chromatography
  10. washeluting with MeOH/DCM (1/30)

Sources & evidence

ORD record
ord-39cddb35f9984d72ac1ec3f647353d21
Source dataset
uspto-grants-2015_03
Patent number
US08993580B2

Reaction notes

Loading…