Sodium Carbonate → (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-neopentyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea

HRID 1626552Notes

Reaction equation

HRID 1626552 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]2[CH3:22])[C:5]2[CH2:10][N:9]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:8][C:6]=2[N:7]=1.[CH:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1.C([O-])([O-])=O.[Na+].[Na+]>COC1CCCC1.CCO.O.O.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([C:2]3[N:3]=[C:4]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]4[CH3:22])[C:5]4[CH2:10][N:9]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:8][C:6]=4[N:7]=3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 44119149N-Cyclopropyl-N'-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 86663152(S)-4-(2-chloro-6-neopentyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine2×

Product 1

HCID 46912284(S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-neopentyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)ureaYield 18.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 131731673CPME EtOH WaterSolvent

Procedure

(S)-4-(2-chloro-6-neopentyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine (intermediate 7) (assumed 0.56 mmol) was stirred in CPME:EtOH:Water (7:3:2, freshly mixed, 2 mL) with 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (203 mg, 0.67 mmol), Pd(PPh3)2Cl2 (20 mg, 0.028 mmol) and Na2CO3 (89 mg, 0.84 mmol) under a stream of nitrogen for 5 min, then irradiated in the microwave at 130° C. for 30 min. The reaction mixture was diluted with water and EtOAc and passed through a celite cartridge. The organic layer was concentrated in vacuo and purified by prep HPLC to give the desired compound as a yellow solid (48 mg, 0.103 mmol, 18% yield over three steps).

Workup

  1. additionfreshly mixed
  2. customirradiated in the microwave at 130° C. for 30 min
  3. concentrationThe organic layer was concentrated in vacuo
  4. custompurified by prep HPLC

Sources & evidence

ORD record
ord-d7e87a0db2664df294f91efa8687efa1
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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