Hydroxyphenylacetic acid → 1,1-Dimethylethyl (1R)-1-(4-hydroxyphenyl)-2-oxo-2-[(6-oxo-2-Phenyl-5,6-dihydro-1H-[1,2]diazepino[4,5,6-cd]indol-8-yl)amino]ethylcarbamate

HRID 720134Notes

Reaction equation

HRID 720134 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:20](=[O:21])[NH:19][N:18]=[CH:17][C:6]3=[C:7]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)[NH:8][C:9]([CH:10]=1)=[C:5]23.OC1C=CC(CC(O)=O)=CC=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[CH3:64][C:65]([O:68][C:69]([NH:71][C@H:72]([C:76]1[CH:81]=[CH:80][C:79]([OH:82])=[CH:78][CH:77]=1)[C:73](O)=[O:74])=[O:70])([CH3:67])[CH3:66]>C(Cl)Cl.CN(C)C=O>[OH:82][C:79]1[CH:80]=[CH:81][C:76]([C@@H:72]([NH:71][C:69](=[O:70])[O:68][C:65]([CH3:66])([CH3:64])[CH3:67])[C:73](=[O:74])[NH:1][C:2]2[CH:3]=[C:4]3[C:20](=[O:21])[NH:19][N:18]=[CH:17][C:6]4=[C:7]([C:11]5[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=5)[NH:8][C:9]([CH:10]=2)=[C:5]34)=[CH:77][CH:78]=1

Participants

8

Reactant 5

HCID 127Hydroxyphenylacetic acidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 11821572Boc-4-hydroxy-D-phenylglycineHCID 1357740798-Amino-2-phenyl-1,5-dihydro-[1,2]diazepino[4,5,6-cd]indol-6-one

Product 1

HCID 1361816521,1-Dimethylethyl (1R)-1-(4-hydroxyphenyl)-2-oxo-2-[(6-oxo-2-Phenyl-5,6-dihydro-1H-[1,2]diazepino[4,5,6-cd]indol-8-yl)amino]ethylcarbamateYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Preparation of example 153 from the title compound of Example 7 (hydrochloride) (42 mg, 0.134 mmol), (2R)-({[(1,1-dimethylethyl)oxy]carbonyl)}amino)(4-hydroxyphenyl)ethanoic acid (54 mg, 0.202 mmol), triethylamine (0.056 mL, 0.402 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (77 mg, 0.202 mmol) in CH2Cl2 (0.4 mL) and N,N-dimethylformamide (0.4 mL) was carried out analogously to Example 11. Additional (2R)-({[(1,1-dimethylethyl)oxy]carbonyl}amino)(4-hydroxyphenyl)ethanoic acid (27 mg, 0.10 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (39 mg, 0.10 mmol) were added after 24 hours to drive the reaction to completion. Silica gel chromatography (eluted with 1:1 hexane:acetone), also in an analogous manner, afforded the title compound (48 mg, 0.091 mmol) as a yellow powder in 68% yield.

Workup

  1. customthe reaction to completion
  2. washSilica gel chromatography (eluted with 1:1 hexane:acetone)

Sources & evidence

ORD record
ord-7a7ae038290d482c8bdff71b426230c2
Source dataset
uspto-grants-2006_11
Patent number
US07132533B2

Reaction notes

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