1-Cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea → (S)-methyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate

HRID 1626675Notes

Reaction equation

HRID 1626675 reaction equation
[CH:1]1([NH:4][C:5](=[O:36])[NH:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[C:16]4[CH2:21][N:20]([C:22]([O:24][C:25](C)(C)C)=[O:23])[CH2:19][C:17]=4[N:18]=3)=[C:9]([F:35])[CH:8]=2)[CH2:3][CH2:2]1.Cl[C:38]1N=C(N2CCOC[C@@H]2C)C2CN(C(OC)=O)CC=2N=1.C1(NC(NC2C=CC(B3OC(C)(C)C(C)(C)O3)=C(F)C=2)=O)CC1>>[CH:1]1([NH:4][C:5](=[O:36])[NH:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([N:29]4[CH2:30][CH2:31][O:32][CH2:33][C@@H:34]4[CH3:38])[C:16]4[CH2:21][N:20]([C:22]([O:24][CH3:25])=[O:23])[CH2:19][C:17]=4[N:18]=3)=[C:9]([F:35])[CH:8]=2)[CH2:2][CH2:3]1

Participants

4

Reactant 3

HCID 666792291-Cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2×HCID 66687725tert-Butyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylateHCID 86663170(S)-methyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate2×

Product 1

HCID 66679219(S)-methyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylateYield 10%

Procedure

Method as described for tert-Butyl 2-(4-(3-(cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (example 143) using (S)-methyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 26) (193 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 brown solid. The solid was purified by prep. HPLC at low pH to afford a colourless solid (22 mg, 10%).

Workup

  1. customReaction mixture
  2. customwas partitioned between EtOAc (50 ml) and water (35 ml)
  3. concentrationconcentrated in vacuo
  4. customto leave a brown solid
  5. customThe solid was purified by prep

Sources & evidence

ORD record
ord-e4bfa360aa384341bac582fe6b608772
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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