Phenyl triflimide → HCID 16062137, compound

HRID 1817701Notes

Reaction equation

HRID 1817701 reaction equation
C(OC([N:8]1[CH2:32][CH2:31][C:11]2[N:12]=[C:13]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:14]=[C:15](OS(C(F)(F)F)(=O)=O)[C:10]=2[CH2:9]1)=O)(C)(C)C.C(OC(N1CCC2N=C(C[C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)N=C(O)C=2C1)=O)(C)(C)C.CC([O-])(C)C.[K+].C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)[F:75])(=O)=O)=CC=1>C1COCC1.O>[CH2:24]([C:13]1[N:14]=[C:15]([C:53]2[CH:54]=[CH:55][C:50]([F:75])=[CH:51][CH:52]=2)[C:10]2[CH2:9][NH:8][CH2:32][CH2:31][C:11]=2[N:12]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 142176Phenyl triflimideHCID 23665647Potassium tert-butoxideHCID 86610326HCID 86610326, compoundHCID 178451651HCID 178451651, compound

Product 1

HCID 16062137HCID 16062137, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Benzyl-4-trifluoromethanesulfonyloxy-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester. To a solution of 2-benzyl-4-hydroxy-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester (2.0 g, 5.9 mmol; prepared from 2-phenyl-acetamidine hydrochloride as described in Example 1, Step A) in THF (15 mL) was added KOtBu (0.408 g, 3.6 mmol). After 15 min, the mixture was treated with N-phenyl-bis(trifluoromethanesulfonimide) (1.18 g, 3.3 mmol) and the mixture was stirred for 18 h. The mixture was diluted with water and extracted with EtOAc (2×). The combined organic layers were dried and concentrated. The resulting residue was purified via SiO2 chromatography (10-40% EtOAc/hexanes) to give 1.15 g (81%) of the title compound which was contaminated with byproducts from N-phenyl-bis(trifluoromethanesulfonimide). Step B. 2-Benzyl-4-(4-fluoro-phenyl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester. The title compound was prepared as described in Example 1, Step C. MS (ESI): exact mass calcd. for C25H26FN3O2, 419.20; m/z found, 420.5 [M+H]+. 1H NMR (CDCl3): 7.53 (dd, J=5.3, 8.7, 2H), 7.43-7.41 (m, 2H), 7.31-7.28 (m, 2H), 7.23-7.14 (m, 3H), 4.55 (s, 2H), 4.27 (s, 2H), 3.75 (t, J=6.1, 2H), 3.00 (t, J=6.0, 2H), 1.43 (s, 9H). Step C. 2-Benzyl-4-(4-fluoro-phenyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine. A solution of the product from Step B (0.131 g, 0.312 mmol) in CH2Cl2 was treated with TFA. After stirring for 4 h, the mixture was concentrated and partitioned between saturated (satd.) aq. NaHCO3 and CH2Cl2 (2×). The combined organic layers were dried and concentrated. The resulting residue was purified via SiO2 chromatography (1-7% 2 M NH3 in MeOH/CH2Cl2) to give 0.084 g (84%) of the title compound. MS (ESI): exact mass calcd. for C20H18FN3, 319.15; m/z found, 320.4 [M+H]+. 1H NMR (CDCl3): 7.51 (dd, J=5.4, 8.8, 2H), 7.41 (d, J=7.4, 2H), 7.31-7.27 (m, 2H), 7.22-7.19 (m, 1H), 7.15 (dd, J=8.7, 2H), 4.27 (s, 2H), 3.95 (s, 2H), 3.24 (t, J=6.1, 2H), 2.97 (t, J=6.1, 2H). Unless otherwise specified, the compounds in Examples 3-57 were prepared using methods similar to those described in Examples 1 and 2, utilizing the appropriate β-ketoesters, amidine hydrochlorides, and arylboronic acids.

Workup

  1. extractionextracted with EtOAc (2×)
  2. customThe combined organic layers were dried
  3. concentrationconcentrated
  4. customThe resulting residue was purified via SiO2 chromatography (10-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-fdb8292350cd48feb5a1eecedefc6c58
Source dataset
uspto-grants-2009_10
Patent number
US07598255B2

Reaction notes

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