Triethylamine → Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate

HRID 492740Notes

Reaction equation

HRID 492740 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15](C2C=CN=C(C(O)=O)C=2)=[CH:14][C:13]=1[F:27])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28]([N:30]([CH2:33][CH3:34])[CH2:31][CH3:32])[CH3:29].[CH3:35][Si:36]([CH3:41])([CH3:40])[CH2:37][CH2:38][OH:39].C1(P([N:56]=[N+]=[N-])(C2C=CC=CC=2)=[O:49])C=CC=CC=1.C[N:60]1[CH2:64][CH2:63][CH2:62][C:61]1=[O:65]>>[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:49][C:62]2[CH:29]=[CH:28][N:30]=[C:64]([NH:60][C:61](=[O:65])[O:39][CH2:38][CH2:37][Si:36]([CH3:41])([CH3:40])[CH3:35])[CH:63]=2)=[CH:14][C:13]=1[F:27])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[NH2:56][C:33]1[CH:34]=[C:38]([O:39][C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[C:13]([F:27])[CH:14]=2)[CH:32]=[CH:31][N:30]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 13387N-methyl-2-pyrrolidoneHCID 180132-(Trimethylsilyl)ethanolHCID 199401P,P-Diphenylphosphinic azideHCID 231533734-(4-Benzyloxycarbonylamino-3-fluorophenyl)pyridine-2-carboxylic acid

Product 2

HCID 57470855Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamateYield 23.5%HCID 576774682-(Trimethylsilyl)ethyl [4-(4-benzyloxycarbonylamino-3-fluorophenoxy)pyridin-2-yl]carbamateYield 20.2%

Conditions

Temperature
90 °C

Procedure

To a solution of 4-(4-benzyloxycarbonylamino-3-fluorophenyl)pyridine-2-carboxylic acid (2.85 g) in N-methylpyrrolidone (30 ml) were added triethylamine (2.59 ml) and 2-(trimethylsilyl)ethanol (1.28 ml), and then diphenylphosphoryl azide (2.59 ml) was added thereto, followed by stirring under a nitrogen atmosphere at room temperature for 1 hr and at 90° C. for 2 hrs. The reaction mixture was cooled down to room temperature and partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (100 ml). The organic layer was washed with brine. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:1 to 1:2, ethyl acetate, then ethyl acetate:methanol=20:1 to 10:1). Fractions containing the two respective target compounds were concentrated respectively to provide 2-(trimethylsilyl)ethyl [4-(4-benzyloxycarbonylamino-3-fluorophenoxy)pyridin-2-yl]carbamate (Production Example 119-2: 747 mg, 20.2%) as a yellow solid, and benzyl [4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate (Production Example 119-1: 618 mg, 23.5%) as a brown solid.

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. custompartitioned between ethyl acetate (100 ml)
  3. washThe organic layer was washed with brine
  4. customThe solvent was evaporated
  5. customto give a residue, which
  6. customwas then purified by silica gel column chromatography (eluent
  7. additionFractions containing the two respective target compounds
  8. concentrationwere concentrated respectively

Sources & evidence

ORD record
ord-e501abcfa6d0447cba32b504795fe803
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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