2-Bromopyrimidine → HCID 71224477, compound

HRID 710022Notes

Reaction equation

HRID 710022 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[NH2:35][C:36]1[CH:37]=[C:38]([CH:51]=[CH:52][C:53]=1[N:54]1[CH2:59][CH2:58][N:57]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[CH3:66])[CH2:56][CH2:55]1)[C:39]([NH:41][CH2:42][CH2:43][CH2:44][N:45]1[CH2:49][CH2:48][CH2:47][C:46]1=[O:50])=[O:40].Br[C:68]1[N:73]=[CH:72][CH:71]=[CH:70][N:69]=1>CC(O)(C)C.C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[O:50]=[C:46]1[CH2:47][CH2:48][CH2:49][N:45]1[CH2:44][CH2:43][CH2:42][NH:41][C:39](=[O:40])[C:38]1[CH:51]=[CH:52][C:53]([N:54]2[CH2:59][CH2:58][N:57]([C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=3[CH3:66])[CH2:56][CH2:55]2)=[C:36]([NH:35][C:68]2[N:73]=[CH:72][CH:71]=[CH:70][N:69]=2)[CH:37]=1

Participants

6

Reactant 3

HCID 783452-BromopyrimidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86675894HCID 86675894, compound

Product 1

HCID 71224477HCID 71224477, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22595558Toluene tert-butyl alcoholSolvent

Procedure

N-[3-(2-Oxo-pyrrolidin-1-yl)-propyl]-3-(pyrimidin-2-ylamino)-4-(4-o-tolyl-piperazin-1-yl)-benzamide (compound no. 242) was prepared as follows: In a microwavable glass tube, Pd(OAc)2 (0.0025 g, 0.0115 mmol) and X—PHOS (5.4 mg, 0.0115 mmol) were taken in a mixture of t-BuOH:toluene (1:5) (2.0 mL) and stirred. This solution was evacuated for 5 min and purged with nitrogen. 3-Amino-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide (0.05 g, 0.115 mmol) and 2-bromo-pyrimidine (2.7 mg, 0.172 mmol) were added to this, evacuated and nitrogen purged. This mixture was stirred at 140° C. under MW for 30 min. LC-MS indicated the product formation along with some other by-products. The reaction mixture was concentrated, dissolved in methanol and purified on preparative HPLC using water/methanol as eluent to give desire product (10.0 mg, 17%).

Workup

  1. customThis solution was evacuated for 5 min
  2. custompurged with nitrogen
  3. customevacuated
  4. customnitrogen purged
  5. stirringThis mixture was stirred at 140° C. under MW for 30 min
  6. concentrationThe reaction mixture was concentrated
  7. dissolutiondissolved in methanol
  8. custompurified on preparative HPLC

Sources & evidence

ORD record
ord-2ac06b568ba344d1933e9b7e3abee59e
Source dataset
uspto-grants-2015_11
Patent number
US09181226B2

Reaction notes

Loading…