Dichloromethane → (S)-1-(3-fluoro-4-(6-isopropyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-(2-fluoroethyl)urea

HRID 1626710Notes

Reaction equation

HRID 1626710 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]2[CH3:20])[C:5]2[CH2:10][N:9]([CH:11]([CH3:13])[CH3:12])[CH2:8][C:6]=2[N:7]=1.[F:21][C:22]1[CH:23]=[C:24]([NH:37][C:38]([NH:40][CH2:41][CH2:42][F:43])=[O:39])[CH:25]=[CH:26][C:27]=1B1OC(C)(C)C(C)(C)O1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>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].CCO.O.COCCOC>[F:21][C:22]1[CH:23]=[C:24]([NH:37][C:38]([NH:40][CH2:41][CH2:42][F:43])=[O:39])[CH:25]=[CH:26][C:27]=1[C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]2[CH3:20])[C:5]2[CH2:10][N:9]([CH:11]([CH3:13])[CH3:12])[CH2:8][C:6]=2[N:7]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 86663166(S)-4-(2-chloro-6-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine2×HCID 86663172N-(2-Fluoroethyl)-N′-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea2×

Product 1

HCID 86663179(S)-1-(3-fluoro-4-(6-isopropyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-(2-fluoroethyl)ureaYield 8.1%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of (S)-4-(2-chloro-6-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine (intermediate 22) (120 mg, 0.404 mmol), 1-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(2-fluoroethyl)urea (intermediate 31) (145 mg, 0.445 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (16 mg, 0.02 mmol) and sodium carbonate (128 mg, 1.21 mmol) in 2 ml of a 7:3:1 mixture of DME:H2O:EtOH respectively was heated in the microwave at 140° C. for 1 hour. The reaction was filtered through celite and purified via preparative HPLC at high pH to yield the title compound (15 mg, 8%).

Workup

  1. filtrationThe reaction was filtered through celite
  2. custompurified via preparative HPLC at high pH

Sources & evidence

ORD record
ord-1ca22ac0c7f746e3b19bf4f545e94484
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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