Triethylamine → (R)-4-(2-oxo-1,2-dihydropyrido[3,4-d]pyrimidin-3(4H)-yl)-N-(2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)piperidine-1-carboxamide

HRID 1453962Notes

Reaction equation

HRID 1453962 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH2:19][C:20]([F:23])([F:22])[F:21])[C:3]1=[O:24].C1C([N+]([O-])=O)=CC=C([Cl-][C:35]([O-])=[O:36])C=1.C(N(CC)CC)C.OC(C(F)(F)F)=O.OC(C(F)(F)F)=O.[NH:59]1[CH2:64][CH2:63][CH:62]([N:65]2[CH2:70][C:69]3[CH:71]=[CH:72][N:73]=[CH:74][C:68]=3[NH:67][C:66]2=[O:75])[CH2:61][CH2:60]1>O1CCCC1>[O:75]=[C:66]1[NH:67][C:68]2[CH:74]=[N:73][CH:72]=[CH:71][C:69]=2[CH2:70][N:65]1[CH:62]1[CH2:61][CH2:60][N:59]([C:35]([NH:1][C@@H:2]2[N:8]=[C:7]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:6]3[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=3[N:4]([CH2:19][C:20]([F:21])([F:23])[F:22])[C:3]2=[O:24])=[O:36])[CH2:64][CH2:63]1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 107353833-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneHCID 1317272423-piperidin-4-yl-3,4-dihydropyrido[3,4-d]pyrimidin-2(1H)-one bisTFA salt

Product 1

HCID 11157626(R)-4-(2-oxo-1,2-dihydropyrido[3,4-d]pyrimidin-3(4H)-yl)-N-(2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)piperidine-1-carboxamideYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3R) 3-amino-2-oxo-5-phenyl-1-(2,2,2-trifluorethyl)-2,3-dihydro-1H-1,4-benzodiazepine (0.030 g, 0.090 mmol) and 4-nitrophenylchloroformate (0.018 g, 0.090 mmol) in dry tetrahydrofuran (2 mL) was cooled to 0° C. under argon. Triethylamine (0.013 mL, 0.090 mmol) was added and the reaction stirred for 1 h. Solid 3-piperidin4-yl-3,4-dihydropyrido[3,4-d]pyrimidin-2(1H)-one bisTFA salt (0.90 mmol) followed by triethylamine (0.065 mL) were added. The reaction was allowed to come to room temperature and stirred for 1 h. The reaction was quenched with 1N NaOH and concentrated. The crude product was purified by chromatography (silica gel, 0 to 10% methanol in methylene chloride gradient elution), to give the title compound (0.014 g, 27% yield). MS 592.2276 (M+1).

Workup

  1. additionwere added
  2. customto come to room temperature
  3. stirringstirred for 1 h
  4. customThe reaction was quenched with 1N NaOH
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography (silica gel, 0 to 10% methanol in methylene chloride gradient elution)

Sources & evidence

ORD record
ord-d418df4171ed490ea826ba1f45829011
Source dataset
uspto-grants-2009_01
Patent number
US07476665B2

Reaction notes

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