1-(2,3-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-ethylurea → (S)-1-(2,3-difluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea

HRID 1626669Notes

Reaction equation

HRID 1626669 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[C:5]2[CH2:10][N:9]([CH3:11])[CH2:8][C:6]=2[N:7]=1.[F:19][C:20]1[C:25]([F:26])=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:22][C:21]=1[NH:36][C:37]([NH:39][CH2:40][CH3:41])=[O:38]>>[F:19][C:20]1[C:25]([F:26])=[C:24]([C:2]2[N:3]=[C:4]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]3[CH3:18])[C:5]3[CH2:10][N:9]([CH3:11])[CH2:8][C:6]=3[N:7]=2)[CH:23]=[CH:22][C:21]=1[NH:36][C:37]([NH:39][CH2:40][CH3:41])=[O:38]

Participants

3

Reactant 2

HCID 666877121-(2,3-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-ethylureaHCID 86663154(S)-4-(2-chloro-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine2×

Product 1

HCID 66679231(S)-1-(2,3-difluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylureaYield 4.2%

Procedure

Method as example 47 using (S)-4-(2-chloro-6-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine (intermediate 12) and 1-(2,3-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-ethylurea as starting materials. The mixture was filtered through a celite 545 pre-packed cartridge (2.5 g), washed with MeOH and the solvent removed in vacuo. The crude material was purified first by Flash Chromatography using a gradient of 0-40% DCM/MeOH, then prep. HPLC at low pH yielding the title compound (8.7 mg, 0.01 mmol, 4.2%).

Workup

  1. filtrationThe mixture was filtered through a celite 545 pre-packed cartridge (2.5 g)
  2. washwashed with MeOH
  3. customthe solvent removed in vacuo
  4. customThe crude material was purified first by Flash Chromatography

Sources & evidence

ORD record
ord-e45c1fef89884349a752f33803bb2067
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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