Diisopropylethylamine → Ethyl(1-{2-[5-(2-bromophenyl)-7-chloro-1-isobutyl-2-oxo-1,2,4,5-tetrahydrobenzo[d]azepin-3-yl]-acetyl}piperidin-4-yl)acetate

HRID 1444834Notes

Reaction equation

HRID 1444834 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:14][N:13]([CH2:15][C:16]([OH:18])=O)[C:12](=[O:19])[CH:11]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:10]2[CH:24]=[CH:25][C:26]([Cl:28])=[CH:27][C:9]1=2.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.[NH:63]1[CH2:68][CH2:67][CH:66]([CH2:69][C:70]([O:72][CH2:73][CH3:74])=[O:71])[CH2:65][CH2:64]1>CN(C)C=O>[CH2:73]([O:72][C:70](=[O:71])[CH2:69][CH:66]1[CH2:67][CH2:68][N:63]([C:16](=[O:18])[CH2:15][N:13]2[CH2:14][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Br:1])[C:9]3[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:10]=3[CH:11]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:12]2=[O:19])[CH2:64][CH2:65]1)[CH3:74]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45358839Piperidin-4-yl-acetic acid ethyl ester hydrochlorideHCID 59025465[5-(2-Bromophenyl)-7-chloro-1-isobutyl-2-oxo-1,2,4,5-tetrahydrobenzo[d]azepin-3-yl]acetic acid

Product 1

HCID 59025502Ethyl(1-{2-[5-(2-bromophenyl)-7-chloro-1-isobutyl-2-oxo-1,2,4,5-tetrahydrobenzo[d]azepin-3-yl]-acetyl}piperidin-4-yl)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

150 mg of the compound from Example 6 (0.32 mol) are dissolved in 2 ml of dimethylformamide, and 147 mg of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (0.39 mol) and 67 μl of diisopropylethylamine (50 mg, 0.39 mol) are added. After stirring at room temperature for 30 min, 80 mg of ethyl 4-piperidylacetate hydrochloride (0.39 mol) and a further 135 μl of diisopropylethylamine (100 mg, 0.77 mol) are added. The reaction mixture is stirred at room temperature overnight and then purified directly by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5). 130 mg (65% of theory) of the title compound are obtained.

Workup

  1. stirringThe reaction mixture is stirred at room temperature overnight
  2. custompurified directly by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5)

Sources & evidence

ORD record
ord-b575bdc2959e41709fc4832bcc37ac88
Source dataset
uspto-grants-2010_02
Patent number
US07662956B2

Reaction notes

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