1-Cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea → (S)-1-(4-(6-acetyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-cyclopropylurea

HRID 1626683Notes

Reaction equation

HRID 1626683 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]([C:11](=[O:13])[CH3:12])[CH2:8][C:6]=2[N:7]=1.[CH:21]1([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[C:30]([F:43])[CH:29]=2)=[O:26])[CH2:23][CH2:22]1>>[C:11]([N:9]1[CH2:10][C:5]2[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH3:20])=[N:3][C:2]([C:31]3[CH:32]=[CH:33][C:28]([NH:27][C:25]([NH:24][CH:21]4[CH2:23][CH2:22]4)=[O:26])=[CH:29][C:30]=3[F:43])=[N:7][C:6]=2[CH2:8]1)(=[O:13])[CH3:12]

Participants

3

Reactant 2

HCID 666792291-Cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2×HCID 86663168(S)-1-(2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)ethanone2×

Product 1

HCID 66678971(S)-1-(4-(6-acetyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-cyclopropylureaYield 4%

Procedure

Method as example 143 using (S)-1-(2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)ethanone (intermediate 24) (212 mg, 0.5 mmol) and 1-cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 29) (182 mg, 0.57 mmol) as starting materials. Reaction mixture was partitioned between EtOAc (50 ml) and water (35 ml), the organic layer passed through a hydrophobic frit and concentrated in vacuo to leave a purple solid. The solid was purified by prep. HPLC at high pH to afford a brown/red solid which was re-purified by prep. HPLC at low pH to afford a yellow solid (9 mg, 4%).

Workup

  1. customReaction mixture
  2. customwas partitioned between EtOAc (50 ml) and water (35 ml)
  3. concentrationconcentrated in vacuo
  4. customto leave a purple solid
  5. customThe solid was purified by prep
  6. customHPLC at high pH to afford a brown/red solid which
  7. customwas re-purified by prep

Sources & evidence

ORD record
ord-3c87237d54b54ea2aa64a2fc33493ac9
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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