tert-butyl N-((3-(aminomethyl)phenyl)methyl)carbamate → [3-({[2-(3-Fluoro-phenyl)-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester

HRID 219667Notes

Reaction equation

HRID 219667 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(C1NC=CN=1)(C1NC=CN=1)=O.[C:29]([O:33][C:34](=[O:45])[NH:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH2:43][NH2:44])[CH:38]=1)([CH3:32])([CH3:31])[CH3:30]>C1COCC1.CCOC(C)=O>[C:29]([O:33][C:34](=[O:45])[NH:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH2:43][NH:44][C:14]([C:11]2[CH:12]=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=2)=[O:16])[CH:38]=1)([CH3:32])([CH3:30])[CH3:31]

Participants

6

Reactant 3

HCID 2756043tert-butyl N-((3-(aminomethyl)phenyl)methyl)carbamateHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 450733632-(3-Fluorophenyl)pyrimidine-5-carboxylic acid

Product 1

HCID 69122649[3-({[2-(3-Fluoro-phenyl)-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl esterYield 81.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (0.5 g, 2.25 mmol) in THF (25 mL) is added carbonyl diimidazole (0.5 g, 2.7 mmol) and heated at 60° C. for 2 hours. The mixture is cooled to room temperature and (3-aminomethyl-benzyl)-carbamic acid tert-butyl ester (0.67 mL, 2.7 mmol) is added. The mixture is stirred for 12 h, diluted with EtOAc (100 mL), washed with brine (2×50 mL), dried with Na2SO4, filtered and concentrated in vacuo. The residue is purified by flash chromatography eluting with 20%-80% EtOAc/heptane to afford [3-({[2-(3-fluoro-phenyl)-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (0.8 g, 80%) as a solid. MS: 437 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 1.35 (s, 9H), 4.13 (d, J=6.1 Hz, 2H), 4.54 (d, J=5.9 Hz, 2H), 7.27-7.48 (m, 4H), 7.62 (m, 1H), 8.16 (m, 1H), 8.31 (m, 1H), 9.32 (s, 2H), 9.43 (m, 1H).

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. washwashed with brine (2×50 mL)
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash chromatography
  7. washeluting with 20%-80% EtOAc/heptane

Sources & evidence

ORD record
ord-ec7ce7f03451493ebee4e8adbb368908
Source dataset
uspto-grants-2012_06
Patent number
US08202863B2

Reaction notes

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