(3-Acetyl-indol-1-yl)-acetic acid → (1S,2S,5R)-3-[2-(3-Acetyl-indol-1-yl)-acetyl]-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid [(S)-1-(3-chloro-2-fluoro-phenyl)-2hydroxy-ethyl]-amide

HRID 1527584Notes

Reaction equation

HRID 1527584 reaction equation
ClC1C(F)=C(C=CC=1)CNC([C@@H]1C[C@]2(CO)[C@@H](C2)N1C(=O)CN1C2=NC=CC=C2C(C(=O)C)=C1)=O.C(O[C:41]([N:43]1[CH2:48][C@H:47]2[C@H:45]([CH2:46]2)[C@H:44]1[C:49](=[O:62])[NH:50][C@@H:51]([C:54]1[CH:59]=[CH:58][CH:57]=[C:56]([Cl:60])[C:55]=1[F:61])[CH2:52][OH:53])=[O:42])(C)(C)C.[C:63]([C:66]1[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[N:68]([CH2:75]C(O)=O)[CH:67]=1)(=[O:65])[CH3:64]>CCOC(C)=O>[Cl:60][C:56]1[C:55]([F:61])=[C:54]([C@H:51]([NH:50][C:49]([C@H:44]2[N:43]([C:41](=[O:42])[CH2:75][N:68]3[C:69]4[C:74](=[CH:73][CH:72]=[CH:71][CH:70]=4)[C:66]([C:63](=[O:65])[CH3:64])=[CH:67]3)[CH2:48][C@H:47]3[C@@H:45]2[CH2:46]3)=[O:62])[CH2:52][OH:53])[CH:59]=[CH:58][CH:57]=1

Participants

5

Reactant 3

HCID 1088616(3-Acetyl-indol-1-yl)-acetic acidHCID 68283613(1S,2S,5R)-2-[(S)-1-(3-chloro-2-fluoro-phenyl)-2-hydroxy-ethylcarbamoyl]-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl esterHCID 68283700(1R,3S,5S)-2-[2-(3-acetyl-pyrrolo[2,3-b]pyridin-1-yl)-acetyl]-5-hydroxymethyl-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid 3-chloro-2-fluoro-benzylamide

Product 1

HCID 71042476(1S,2S,5R)-3-[2-(3-Acetyl-indol-1-yl)-acetyl]-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid [(S)-1-(3-chloro-2-fluoro-phenyl)-2hydroxy-ethyl]-amide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

The title compound was prepared in 2 steps according to the procedure described for the preparation of Example 610 (1R,3S,5S)-2-[2-(3-acetyl-pyrrolo[2,3-b]pyridin-1-yl)-acetyl]-5-hydroxymethyl-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid 3-chloro-2-fluoro-benzylamide from (1S,2S,5R)-2-[(S)-1-(3-chloro-2-fluoro-phenyl)-2-hydroxy-ethylcarbamoyl]-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (prepared using similar protocols as described in Scheme B9) and (3-acetyl-indol-1-yl)-acetic acid. White powder. TLC, Rf (EtOAc)=0.10; MS (UPLC/MS): 498.3/500.4 [M+H]+, 542.4/544.3 [M+HCOO]−; tR (HPLC conditions a): 3.10 min.

Workup

  1. custom3.10 min.

Sources & evidence

ORD record
ord-1ec4cae19bd54007a2130e3d95b8c090
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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