(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acid → [2-(3-{4-[3-(5-Chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenylcarbamoyl}-morpholin-4-yl)-2-oxo-1-phenyl-ethyl]-carbamic acid tert-butyl ester

HRID 2075775Notes

Reaction equation

[C:1]([O:5][C:6](=[O:48])[NH:7][CH:8]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:9](N1CCCCC1C(=O)NC1C=CC(C#CC2C(C3C=C(C)C=CC=3O)=NN(C)C=2)=CC=1)=[O:10])([CH3:4])([CH3:3])[CH3:2].[Cl:49][C:50]1[CH:51]=[CH:52][C:53]([OH:79])=[C:54]([C:56]2[C:60]([C:61]#[C:62][C:63]3[CH:68]=[CH:67][C:66]([NH:69][C:70]([CH:72]4[CH2:77][O:76][CH2:75][CH2:74][NH:73]4)=[O:71])=[CH:65][CH:64]=3)=[CH:59][N:58]([CH3:78])[N:57]=2)[CH:55]=1.N(C(OC(C)(C)C)=O)[C@@H](C(O)=O)C1C=CC=CC=1>>[C:1]([O:5][C:6](=[O:48])[NH:7][CH:8]([C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[C:9]([N:73]1[CH2:74][CH2:75][O:76][CH2:77][CH:72]1[C:70](=[O:71])[NH:69][C:66]1[CH:65]=[CH:64][C:63]([C:62]#[C:61][C:60]2[C:56]([C:54]3[CH:55]=[C:50]([Cl:49])[CH:51]=[CH:52][C:53]=3[OH:79])=[N:57][N:58]([CH3:78])[CH:59]=2)=[CH:68][CH:67]=1)=[O:10])([CH3:4])([CH3:2])[CH3:3]

Participants

Reactant 3

HCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acid

HCID 135974951[2-(2-{4-[3-(2-Hydroxy-5-methyl-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenylcarbamoyl}-piperidin-1-yl)-2-oxo-1-phenyl-ethyl]-carbamic acid tert-butyl ester

HCID 136346686Morpholine-3-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenyl}-amide

Product 1

HCID 136346688[2-(3-{4-[3-(5-Chloro-2-hydroxy-phenyl)-1-methyl-1H-pyrazol-4-ylethynyl]-phenylcarbamoyl}-morpholin-4-yl)-2-oxo-1-phenyl-ethyl]-carbamic acid tert-butyl ester

Procedure

Using the same procedure for the preparation of 3D, reaction of compound 7D with BOC-D-Phg-OH (2D) afforded the title compound 8D, which was purified by silica column chromatography eluting with dichloromethane/EtOAc (9/1, 8/1, 7/1) to give pure 8D as white powder in similar yield. 1H NMR (CDCl3, 500 MHz) δ 10.68 (s, 1H), 8.72 (s, 1H), 8.61 (s, 1H), 7.92 (d, 2H, J=7.0 Hz), 7.63 (s, 1H), 7.57 (d, 2H, J=8.0 Hz), 7.43 (m, 5H), 7.20 (d, 1H, J=8.5 Hz), 6.97 (dd, 1H, J=9.0, 1.0 Hz), 5.48 (d, 1H, J=6.0 Hz), 5.40 (d, 1H, J=5.5 Hz), 5.29 (s, 1H), 4.82 (d, 1H, J=12.0 Hz), 3.96 (s, 3H), 3.78 (d, 1H, J=10.5 Hz), 3.65 (t, 1H, J=12.5 Hz), 3.60 (t, 1H, J=10.0 Hz), 3.43 (dd, 1H, J=11.5, 2.0 Hz), 3.07 (t, 1H, J=11.5 Hz), 1.45 (s, 9H). LCMS (ESI) m/z 692.34 (MNa+), 670.33 (MH+), 614.24 (100), 570.23. HPLC: tR=5.35 min.

Sources & evidence

ORD record: ord-dc65977969284a358846eb8f762a2b96
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07923004B2

Reaction notes

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