tert-butyl N-((3-(aminomethyl)phenyl)methyl)carbamate → [3-({[2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester

HRID 219661Notes

Reaction equation

HRID 219661 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(C1NC=CN=1)(C1NC=CN=1)=O.[C:30]([O:34][C:35](=[O:46])[NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][NH2:45])[CH:39]=1)([CH3:33])([CH3:32])[CH3:31]>C1COCC1.CCOC(C)=O>[C:30]([O:34][C:35](=[O:46])[NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][NH:45][C:15]([C:11]2[C:12]([CH3:14])=[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:17])[CH:39]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

6

Reactant 3

HCID 2756043tert-butyl N-((3-(aminomethyl)phenyl)methyl)carbamateHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acid

Product 1

HCID 69123142[3-({[2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (0.195 g, 0.89 mmol) in THF (5 mL) is added carbonyl diimidazole (0.18 g, 1.1 mmol) and heated at 60° C. for 2 hours. The mixture is cooled to room temperature. (3-Aminomethyl-benzyl)-carbamic acid tert-butyl ester (0.25 mL, 1.1 mmol) is added and the mixture is stirred for 12 hours. The mixture is 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)-4-methyl-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (0.32 g, 80%) as a solid. MS: 451 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 1.38 (s, 9H), 2.65 (s, 3H), 4.14 (d, J=6.1 Hz, 2H), 4.50 (d, J=5.6 Hz, 2H), 7.15 (m, 1H), 7.24 (m, 1H), 7.31 (m, 1H), 7.43 (m, 1H), 7.62 (m, 1H), 8.13 (m, 1H), 8.28 (m, 1H), 8.89 (s, 1H), 9.23 (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-a3c7bf146a2b4e918c7cf096eec293d9
Source dataset
uspto-grants-2012_06
Patent number
US08202863B2

Reaction notes

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