Ammonia → (8-Carbamoylmethyl-7-chloro-naphthalen-2-ylmethyl)-(2-fluoro-ethyl)-carbamic acid tert-butyl ester

HRID 505193Notes

Reaction equation

HRID 505193 reaction equation
C(C1NC=CN=1)(C1[NH:4]C=CN=1)=O.[C:13]([O:17][C:18]([N:20]([CH2:24][C:25]1[CH:34]=[C:33]2[C:28]([CH:29]=[CH:30][C:31]([Cl:39])=[C:32]2[CH2:35][C:36](O)=[O:37])=[CH:27][CH:26]=1)[CH2:21][CH2:22][F:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].N>CN(C=O)C>[C:13]([O:17][C:18](=[O:19])[N:20]([CH2:24][C:25]1[CH:26]=[CH:27][C:28]2[C:33](=[C:32]([CH2:35][C:36](=[O:37])[NH2:4])[C:31]([Cl:39])=[CH:30][CH:29]=2)[CH:34]=1)[CH2:21][CH2:22][F:23])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 86625785(7-{[Tert-butoxycarbonyl-(2-fluoro-ethyl)-amino]-methyl}-2-chloro-naphthalen-1-yl)-acetic acid

Product 1

HCID 86625784(8-Carbamoylmethyl-7-chloro-naphthalen-2-ylmethyl)-(2-fluoro-ethyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Carbonyl diimidazole (95 mg, 0.58 mmol) was added at RT under an atmosphere of argon to a solution of (7-{[tert-butoxycarbonyl-(2-fluoro-ethyl)-amino]-methyl}-2-chloro-naphthalen-1-yl)-acetic acid (210 mg, 0.53 mmol) in DMF (2.0 ml). After 2 h at RT, concentrated aqueous ammonia (4.3 ml) is added, and the mixture is stirred for 15 minutes at RT. The emulsion is extracted with EtOAc. The organic layer is washed with brine and dried over Na2SO4. After concentration, the residue is purified by FCC (EtOAc) to yield the title compound. 1H NMR (d6-DMSO, 400 MHz): δ 1.38+1.46 (2x br s, 9H), 3.3-3.6 (br m, 2H), 4.08 (s, 2H), 4.40-4.65 (br m, 2H), 4.61 (s, 2H), 7.02 (br s, NH), 7.42 (br d, J=9 Hz, 1H), 7.48-7.58 (br m, 3H), 7.80-7.90 (br m, 2H), 7.95 (br d, J=9 Hz, 1H). ES+-MS: 412.3, 414.2 [M+H+H2O]+. ES−-MS: 393.3, 395.3 [M−H]−.

Workup

  1. extractionThe emulsion is extracted with EtOAc
  2. washThe organic layer is washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationAfter concentration
  5. customthe residue is purified by FCC (EtOAc)

Sources & evidence

ORD record
ord-cd372720ef6c4cf1bf33e03c412da0bf
Source dataset
uspto-grants-2010_08
Patent number
US07781438B2

Reaction notes

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