Triethylamine → (R)-4-(2-oxo-1,2-dihydropyrido[2,3-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 1453963Notes

Reaction equation

HRID 1453963 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.[OH:45][C:46]([C:48]([F:51])([F:50])[F:49])=[O:47].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][CH:73]=[N:74][C:68]=3[NH:67][C:66]2=[O:75])[CH2:61][CH2:60]1>O1CCCC1.CS(C)=O>[C:46]([OH:47])([C:48]([F:51])([F:50])[F:49])=[O:45].[O:75]=[C:66]1[NH:67][C:68]2[N:74]=[CH: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

7

Reactant 3

HCID 8471Triethylamine2×HCID 107353833-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneHCID 1317272433-Piperidin-4-yl-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one bisTFA salt

Product 2

HCID 6422Trifluoroacetic acidHCID 11456102(R)-4-(2-oxo-1,2-dihydropyrido[2,3-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 34.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3R) 3-amino-2-oxo-5-phenyl-1-(2,2,2-trifluorethyl)-2,3-dihydro-1H-1,4-benzodiazepine (0.037 g, 0.112 mmol) and 4-nitrophenylchloroformate (0.0238 g, 0.112 mmol) in dry tetrahydrofuran (2 mL) was cooled to 0° C. under argon. Triethylamine (0.011 g, 0.112 mmol) was added and the reaction stirred for 1 h. 3-Piperidin-4-yl-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one bisTFA salt (0.112 mmol) in DMSO (1 mL) followed by triethylamine (0.055 g) in were added. The reaction was allowed to come to room temperature and stirred for 4 h. The reaction was concentrated and purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution) to give TFA salt of the title compound (0.023 g, 29% yield). MS 592.2261 (M+1).

Workup

  1. additionin were added
  2. customto come to room temperature
  3. stirringstirred for 4 h
  4. concentrationThe reaction was concentrated
  5. custompurified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution)

Sources & evidence

ORD record
ord-3d87aaa8e2c445cd8fa8f1a78c7cb8e9
Source dataset
uspto-grants-2009_01
Patent number
US07476665B2

Reaction notes

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