Sodium Carbonate → HCID 68379371, compound

HRID 1410073Notes

Reaction equation

HRID 1410073 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N:18]3[CH2:22][CH2:21][CH2:20][C@@H:19]3[CH3:23])[CH:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[C:34]([CH:50]=[CH:51][CH:52]=2)[CH2:35][NH:36][CH:37]2[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[CH3:23][C@H:19]1[CH2:20][CH2:21][CH2:22][N:18]1[C:14]1[CH:13]=[C:12]([NH:11][C:4]2[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=[C:2]([C:32]3[CH:33]=[C:34]([CH:50]=[CH:51][CH:52]=3)[CH2:35][NH:36][CH:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:48])([CH3:49])[CH3:47])=[O:44])[CH2:39][CH2:38]3)[N:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 68379410HCID 68379410, compoundHCID 86671787HCID 86671787, compound

Product 1

HCID 68379371HCID 68379371, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-5-chloro-N-(3-(2-methylpyrrolidin-1-yl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (200 mg, 0.58 mmol) and crude tert-butyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylamino)piperidine-1-carboxylate in 10 mL of 1,4-dioxane and 2 mL of water was added Na2CO3 (184 mg, 1.74 mmol) followed by Pd(PPh3)4 (184 mg, 0.03 mmol) under nitrogen with stirring. The mixture was refluxed for 15 hours under nitrogen. After cooled, the solvent was evaporated by rotary evaporation under reduced pressure. The residue was poured into water and extracted with EtOAc (3×15 mL). The organic layer was washed with brine and dried over Na2SO4. After filtration and concentration, the residue was purified by column chromatography (silica gel, eluting with EtOAc) to give (S)-tert-butyl 4-(3-(7-(3-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzylamino)piperidine-1-carboxylate (110 mg, 32% for the two steps). LC-MS: 250.6 [M/2+H]+, 600 [M+H]+, tR=1.57 min.

Workup

  1. temperatureThe mixture was refluxed for 15 hours under nitrogen
  2. temperatureAfter cooled
  3. customthe solvent was evaporated by rotary evaporation under reduced pressure
  4. additionThe residue was poured into water
  5. extractionextracted with EtOAc (3×15 mL)
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration and concentration
  9. customthe residue was purified by column chromatography (silica gel, eluting with EtOAc)

Sources & evidence

ORD record
ord-2abc27c7502e4d6d84511a52b2d75f8e
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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