Dichloromethane → HCID 24963249, compound

HRID 2067757Notes

Reaction equation

HRID 2067757 reaction equation
[OH:1][C@H:2]([CH2:32][OH:33])[CH2:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[C:26][Si](C)(C)C)=[CH:21][C:20]=3[F:31])=[C:12]([F:17])[C:13](=[O:16])[N:14]([CH3:15])[C:7]=2[N:6]=[CH:5]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(Cl)Cl>C1COCC1>[OH:1][C@H:2]([CH2:32][OH:33])[CH2:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[CH:26])=[CH:21][C:20]=3[F:31])=[C:12]([F:17])[C:13](=[O:16])[N:14]([CH3:15])[C:7]=2[N:6]=[CH:5]1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 2724141Tetrabutylammonium FluorideHCID 58191930HCID 58191930, compound

Product 1

HCID 24963249HCID 24963249, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (S)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-((trimethylsilyl)ethynyl)phenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 21A in THF (3 mL) was added 1M solution of TBAF (0.14 mL, 0.14 mmol, 1.75 eq). The reaction mixture was stirred at ambient temperature for 1 hour. The solvent was removed under vacuum and the residue was purified by flash chromatography with 2:8 MeOH:DCM to yield the desired product (S)-3-(2,3-dihydroxypropyl)-5-(4-ethynyl-2-fluorophenylamino)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (example 21) as an off-white solid (10 mg, 30% yield). 1H NMR (400 MHz, MeOD) δ ppm 3.54 (s, 1 H) 3.60 (d, J=5.05 Hz, 2 H) 3.72 (s, 3 H) 3.75-3.83 (m, 1 H) 3.93-4.00 (m, 1 H) 4.41 (dd, J=13.52, 2.91 Hz, 1 H) 7.11 (td, J=8.15, 5.68 Hz, 1 H) 7.21-7.29 (m, 2 H) 8.40 (s, 1 H). [M+H] calc'd for C19H16F2N4O4, 403; found, 403.

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue was purified by flash chromatography with 2:8 MeOH

Sources & evidence

ORD record
ord-938db722e7184097967978ed20174761
Source dataset
uspto-grants-2012_10
Patent number
US08293901B2

Reaction notes

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