4-Methylmorpholine → N-[5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]oxalamic acid ethyl ester

HRID 1500012Notes

Reaction equation

HRID 1500012 reaction equation
[F:1][C:2]1[C:3]([NH2:17])=[N:4][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[N:6][CH:7]=1.CN1CCOCC1.[CH2:25]([O:27][C:28](=[O:32])[C:29](Cl)=[O:30])[CH3:26]>C(Cl)Cl>[CH2:25]([O:27][C:28](=[O:32])[C:29]([NH:17][C:3]1[C:2]([F:1])=[CH:7][N:6]=[C:5]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)[N:4]=1)=[O:30])[CH3:26]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 20884Ethoxalyl chlorideHCID 578185745-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine

Product 1

HCID 57818548N-[5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]oxalamic acid ethyl esterYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.235 g, 0.99 mmol), N-methyl morpholine on polystyrene (0.538 g, 1.24 mmol), and CH2Cl2 (5 mL) was added chloro-oxo-acetic acid ethyl ester (0.135 g, 0.99 mmol) and the resulting mixture was agitated on an orbital shaker for 16 h. The reaction contents were filtered onto an acidic SPE cartridge and eluted with CH2Cl2. The CH2Cl2 filtrate was evaporated to give 0.165 g (50%) of N-[5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]oxalamic acid ethyl ester as a clear oil: 1H NMR (300 MHz, CDCl3) δ 9.21 (bs, 1H), 8.38 (d, J=2.3 Hz, 1H), 7.48 (m, 2H), 7.03 (t, J=8.5 Hz, 2H), 5.40 (s, 2H), 4.48 (q, J=7.1 Hz, 2H), 1.45 (t, J=7.1 Hz, 3H); HPLC-MS (ESI) m/z 338 (M+H)+.

Workup

  1. customThe reaction contents
  2. filtrationwere filtered onto an acidic SPE cartridge
  3. washeluted with CH2Cl2
  4. customThe CH2Cl2 filtrate was evaporated

Sources & evidence

ORD record
ord-0d57e19c0c2241fbaee7bf42902ad438
Source dataset
uspto-grants-2015_12
Patent number
US09204653B2

Reaction notes

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