tert-Butyl methyl ether → 2-(2-Amino-pyrimidin-4-yl)-1-methyl-4-oxo-3-{3-[3-(4-trifluoromethyl-phenyl)-ureido]-benzyl}-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 869326Notes

Reaction equation

HRID 869326 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:8]=[CH:7][C:6]([N+:9]#[C-:10])=[CH:5][CH:4]=1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][C:23]2[N:26]([CH3:44])[C:27]([C:37]3[CH:42]=[CH:41][N:40]=[C:39]([NH2:43])[N:38]=3)=[C:28]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([NH2:36])[CH:31]=3)[C:22]=2[C:21]1=[O:45])=[O:19])([CH3:16])([CH3:15])[CH3:14].CC([O:50]C)(C)C>C(Cl)Cl>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][C:23]2[N:26]([CH3:44])[C:27]([C:37]3[CH:42]=[CH:41][N:40]=[C:39]([NH2:43])[N:38]=3)=[C:28]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([NH:36][C:10]([NH:9][C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:11])([F:12])[F:1])=[CH:8][CH:7]=4)=[O:50])[CH:31]=3)[C:22]=2[C:21]1=[O:45])=[O:19])([CH3:15])([CH3:16])[CH3:14]

Participants

5

Reactant 3

HCID 15413tert-Butyl methyl etherHCID 27594124-(Trifluoromethyl)phenyl isocyanideHCID 672845333-(3-Amino-benzyl)-2-(2-amino-pyrimidin-4-yl)-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 672845022-(2-Amino-pyrimidin-4-yl)-1-methyl-4-oxo-3-{3-[3-(4-trifluoromethyl-phenyl)-ureido]-benzyl}-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Trifluoromethyl-phenyl isocyanide (0.018 g, 0.096 mmol) was added to a solution of 3-(3-Amino-benzyl)-2-(2-amino-pyrimidin-4-yl)-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (0.039 g, 0.088 mmol) (prepared as described in Example 6) in DCM (2.0 ml) and the reaction mixture was stirred at room temperature for 3 h, under an argon atmosphere. MTBE (5.0 ml) was added to the reaction mixture and the organic layer was washed with purite water (1×5.0 ml), brine (1×5.0 ml), dried over Na2SO4. The filtrate was dried under vacuum and the crude was purified by reverse phase chromatography, affording 2-(2-Amino-pyrimidin-4-yl)-1-methyl-4-oxo-3-{3-[3-(4-trifluoromethyl-phenyl)-ureido]-benzyl}-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (0.051 g, 0.080 mmol, 93%).

Workup

  1. washthe organic layer was washed with purite water (1×5.0 ml), brine (1×5.0 ml)
  2. dry with materialdried over Na2SO4
  3. customThe filtrate was dried under vacuum
  4. customthe crude was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-9f58c27ffcd14041b2658781cd42f7a8
Source dataset
uspto-grants-2015_03
Patent number
US08969366B2

Reaction notes

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