Dichloromethane → (S)-1-(4-(4-(3-methylmorpholino)pyrimidin-2-yl)phenyl)-3-(pyridin-4-yl)urea

HRID 1771566Notes

Reaction equation

HRID 1771566 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[CH3:14])[CH:5]=[CH:4][N:3]=1.[N:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28](B3OC(C)(C)C(C)(C)O3)=[CH:27][CH:26]=2)=[O:23])=[CH:17][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:14][C@@H:9]1[N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:28]3[CH:27]=[CH:26][C:25]([NH:24][C:22]([NH:21][C:18]4[CH:17]=[CH:16][N:15]=[CH:20][CH:19]=4)=[O:23])=[CH:30][CH:29]=3)[N:7]=2)[CH2:13][CH2:12][O:11][CH2:10]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666878001-(Pyridin-4-yl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2×HCID 72942067(S)-4-(2-Chloropyrimidin-4-yl)-3-methylmorpholine2×

Product 1

HCID 53379670(S)-1-(4-(4-(3-methylmorpholino)pyrimidin-2-yl)phenyl)-3-(pyridin-4-yl)urea

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

(S)-4-(2-chloropyrimidin-4-yl)-3-methylmorpholine (intermediate 3) (100 mg, 0.47 mmol) was stirred with 1-(pyridin-4-yl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 30) (175 mg, 0.52 mmol), Na2CO3 (149 mg, 1.4 mmol) and Pd(dppf)Cl2:DCM (19 mg, 0.02 mmol) in DME:Water (4:1)(5 ml) for 30 mins at 130° C. in a microwave. The reaction mixture was filtered through a celite545 cake and washed with methanol. The solvent was removed in vacuo and the crude residue was purified by prep HPLC at high pH. Further purification was achieved using an SCX-2 cartridge yielding the title compound. (32 mg, 17%)

Workup

  1. filtrationThe reaction mixture was filtered through a celite545 cake
  2. washwashed with methanol
  3. customThe solvent was removed in vacuo
  4. customthe crude residue was purified by prep HPLC at high pH
  5. customFurther purification

Sources & evidence

ORD record
ord-3663025fa057463b86756095fa7e3500
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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