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

HRID 2075764Notes

Reaction equation

HRID 2075764 reaction equation
[C:1]([O:5][C:6](=[O:50])[NH:7][C@H:8]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:9]([N:11]1[CH2:16][CH2:15]C[CH2:13][C@H:12]1[C:17](=[O:43])[NH:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]#[C:26][C:27]2[C:28]([C:35]3[CH:40]=[C:39]([Cl:41])[CH:38]=[CH:37][C:36]=3[OH:42])=[N:29][N:30]([CH2:32][CH2:33][OH:34])[CH:31]=2)=[CH:21][CH:20]=1)=[O:10])([CH3:4])([CH3:3])[CH3:2].ClC1C=CC(O)=C(C2C(C#CC3C=CC(NC(C4COCCN4)=[O:73])=CC=3)=CN(CCO)N=2)C=1.N(C(OC(C)(C)C)=O)[C@@H](C(O)=O)C1C=CC=CC=1>>[C:1]([O:5][C:6](=[O:50])[NH:7][C@H:8]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:9]([N:11]1[CH2:16][CH2:15][O:73][CH2:13][CH:12]1[C:17](=[O:43])[NH:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]#[C:26][C:27]2[C:28]([C:35]3[CH:40]=[C:39]([Cl:41])[CH:38]=[CH:37][C:36]=3[OH:42])=[N:29][N:30]([CH2:32][CH2:33][OH:34])[CH:31]=2)=[CH:23][CH:24]=1)=[O:10])([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 3

HCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 135974992[2-(2(S)-{4-[3-(5-Chloro-2-hydroxy-phenyl)-1-(2-hydroxy-ethyl)-1H-pyrazol-4-ylethynyl]-phenylcarbamoyl}-piperidin-1-yl)-2-oxo-1(R)-phenyl-ethyl]-carbamic acid tert-butyl esterHCID 135975008HCID 135975008, compound

Product 1

HCID 135975022[2-(3(R,S)-{4-[3-(5-Chloro-2-hydroxy-phenyl)-1-(2-hydroxy-ethyl)-1H-pyrazol-4-ylethynyl]-phenylcarbamoyl}-morpholin-4-yl)-2-oxo-1(R)-phenyl-ethyl]-carbamic acid tert-butyl ester

Procedure

Using the same procedure for the preparation of 12A, reaction of compound 17A with BOC-D-Phg-OH (11A) afforded the title compound 18A, which was purified by silica column chromatography eluting with dichloromethane/acetone (5/1, 4/1, 3/1) to give pure 18A as white powder in similar yield. 1H NMR (CDCl3, 500 MHz) δ 10.677 and 10.668 (both s, total 1H), 9.39 and 8.70 and 8.64 (all s, total 2H), 7.88 (m, 2H), 7.79 and 7.77 (both s, total 1H), 7.56 (m, 2H), 7.43 (m, 5H), 7.19 (d, 1H, J=8.5 Hz), 6.95 (d, 1H, J=8.0 Hz), 5.98 and 5.72 and 5.48 and 5.41 (all d, total 2H, J=6.5-7.5 Hz), 5.28 and 5.13 (both s, total 1H), 4.78 (d, 0.5H, J=12.0 Hz), 4.63 (m, 0.5H), 4.29 (m, 2H), 4.03 (m, 2H), 3.83 and 3.63 and 3.42 and 3.17 and 3.04 (all m, total 5H), 1.94 (s, 1H, 1.51 and 1.45 (both s, total 9H). LCMS (ESI) m/z 722.20 (MNa+), 700.21 (MH+), 644.13 (100), 600.14, 354.07. HPLC: tR=5.18 min.

Sources & evidence

ORD record
ord-151da276bcff4af3a5f80f46b1d4fa97
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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