Dichloromethane → HCID 53379558, compound

HRID 1771560Notes

Reaction equation

HRID 1771560 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:14][CH:13]3[O:15][CH:10]([CH2:11][CH2:12]3)[CH2:9]2)[CH:5]=[CH:4][N:3]=1.[CH2:16]([NH:18][C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][CH:23]=1)=[O:20])[CH3:17].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>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]>[CH:10]12[O:15][CH:13]([CH2:12][CH2:11]1)[CH2:14][N:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:25]3[CH:24]=[CH:23][C:22]([NH:21][C:19]([NH:18][CH2:16][CH3:17])=[O:20])=[CH:27][CH:26]=3)[N:7]=1)[CH2:9]2

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44119377N-Ethyl-N'-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 663715273-(2-Chloropyrimidin-4-yl)-8-oxa-3-azabicyclo[3,2,1]octane2×

Product 1

HCID 53379558HCID 53379558, compound

Reagents, catalysts & solvents 2

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

Procedure

3-(2-chloropyrimidin-4-yl)-8-oxa-3-azabicyclo[3,2,1]octane (intermediate 24) (100 mg, 0.44 mmol) was stirred with 1-ethyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (141 mg, 0.48 mmol), Pd(dppf)Cl2:DCM (18 mg, 0.002) and Na2CO3(140 mg, 1.3 mmol) in DME:Water (4:1) for 30 minutes at 130° C. in microwave conditions. The reaction mixture was filtered through a celite545 cake and washed with methanol. The reaction mixture was concentrated in vacuo. The resulting oil was purified by prep HPLC at low pH to afford the title compound as a white solid. (20 mg, 13%)

Workup

  1. filtrationThe reaction mixture was filtered through a celite545 cake
  2. washwashed with methanol
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customThe resulting oil was purified by prep HPLC at low pH

Sources & evidence

ORD record
ord-768c6b4f279948de851cf04a36db32d5
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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