(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acid → [2-(3(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 2075767Notes

Reaction equation

HRID 2075767 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][O:14][CH2:13][CH: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([C@@H]4COCCN4)=O)=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:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[C:9]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][C@H: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])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 3

HCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 135974932Morpholine-3(S)-carboxylic acid {4-[3-(5-chloro-2-hydroxy-phenyl)-1-(2-hydroxy-ethyl)-1H-pyrazol-4-ylethynyl]-phenyl}-amideHCID 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

Product 1

HCID 135974930[2-(3(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 18A, reaction of compound 21A with BOC-D-Phg-OH (11A) afforded the title compound 22A as a white powder in similar yield. 1H NMR (CDCl3, 500 MHz) δ 10.60 (s, 1H), 8.71 (s, 1H), 8.62 (s, 1H), 7.90 (d, 2H, J=8.5 Hz), 7.78 (s, 1H), 7.56 (d, 2H, J=8.5 Hz), 7.43 (m, 5H), 7.20 (dd, 1H, J=8.5, 1.5 Hz), 6.97 (d, 1H, J=9.0 Hz), 5.48 (d, 1H, J=6.5 Hz), 5.40 (d, 1H, J=6.0 Hz), 5.29 (s, 1H), 4.81 (d, 1H, J=12.0 Hz), 4.31 (t, 2H, J=5.0 Hz), 4.06 (m, 2H), 3.78 (d, 1H, J=10.5 Hz), 3.64 (t, 1H, J=12.5 Hz), 3.59 (t, 1H, J=1.0 Hz), 3.43 (dd, 1H, J=11.0, 2.5 Hz), 3.06 (t, 1H, J=10.5 Hz), 1.93 (t, 1H, J=5.0 Hz), 1.45 (s, 9H). LCMS (ESI) m/z 722.16 (MNa+), 700.18 (MH+), 644.13 (100), 600.11, 354.11. HPLC: tR=4.48 min.

Sources & evidence

ORD record
ord-92f697e258474c0ea09fa1593a5f974c
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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