Triethylamine → {(S)-1-[(R)-1-(3-Amino-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-7-yl)pyrrolidin-3-yl]ethyl}-carbamic acid tert-butyl ester

HRID 10337

Reaction equation

HRID 10337 reaction equation
[NH2:1][N:2]1[C:7](=[O:8])[C:6]2[CH:9]=[C:10]([F:17])[C:11](S(=S)(O)=O)=[N:12][C:5]=2[N:4]([CH:18]2[CH2:20][CH2:19]2)[C:3]1=[O:21].[C:22]([O:26][C:27](=[O:36])[NH:28][C@@H:29]([C@H:31]1[CH2:35][CH2:34][NH:33][CH2:32]1)[CH3:30])([CH3:25])([CH3:24])[CH3:23].C(N(CC)CC)C>C(#N)C>[C:22]([O:26][C:27](=[O:36])[NH:28][C@H:29]([C@@H:31]1[CH2:35][CH2:34][N:33]([C:11]2[C:10]([F:17])=[CH:9][C:6]3[C:7](=[O:8])[N:2]([NH2:1])[C:3](=[O:21])[N:4]([CH:18]4[CH2:20][CH2:19]4)[C:5]=3[N:12]=2)[CH2:32]1)[CH3:30])([CH3:23])([CH3:24])[CH3:25]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10104699(3S,1R)-3-(1-(t-butoxycarbonylamino)ethyl)pyrrolidineHCID 219790013-Amino-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-7-thiosulfonic acid2×

Product 1

HCID 58681891{(S)-1-[(R)-1-(3-Amino-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-7-yl)pyrrolidin-3-yl]ethyl}-carbamic acid tert-butyl esterYield 58.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 0.12 g (0.38 mmol) of 3-amino-1-cyclopropyl-6-fluoro-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-7-thiosulfonic acid (Compound 24c) in 10 mL of acetonitrile is treated with 0.24 g (1.14 mmol) of ((R)-(S)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester (J. Het. Chem., 1992; 29:1481), 0.25 g (2.5 mmol) of triethylamine and stirred at room temperature for 18 hours then 50° C. for 1 hour. The solvent is removed in vacuo and the residue is partitioned between ethyl acetate (50 mL) and water (25 mL). The organic layer is washed with water, dried (MgSO4), filtered and evaporated in vacuo to give 0.28 g. Chromatography on flash grade silica gel (230–400 mesh) column (2×12 cm) eluting with dichloromethane/ethanol (95:5) provided 0.1 g of the title compound, mp 175–177° C.

Workup

  1. wait50° C. for 1 hour
  2. customThe solvent is removed in vacuo
  3. customthe residue is partitioned between ethyl acetate (50 mL) and water (25 mL)
  4. washThe organic layer is washed with water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto give 0.28 g
  9. washChromatography on flash grade silica gel (230–400 mesh) column (2×12 cm) eluting with dichloromethane/ethanol (95:5)

Sources & evidence

ORD record
ord-7617c6a9714f4fc1badb4dccedb07ffc
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Linked notes

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