(1R,2S)-5'-fluoro-2-(1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one → HCID 178517179, compound

HRID 1410353Notes

Reaction equation

HRID 1410353 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[NH:15][C:14]4=[O:22])[CH2:12]3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.[F:23]C1C=C2C(=CC=1)NC(=O)[C@]12C[C@H]1C1C=C2C(C=NN2)=CC=1>>[F:23][C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14](=[O:22])[C@:13]12[CH2:12][C@H:11]1[C:7]1[CH:6]=[C:5]2[C:10]([C:2]([I:1])=[N:3][NH:4]2)=[CH:9][CH:8]=1

Participants

3

Reactant 2

HCID 58486165(1R,2S)-5'-fluoro-2-(1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-oneHCID 178517040(1R*,2S*)-2-(3-iodo-1H-indazol-6-yl)-spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 178517179HCID 178517179, compoundYield 57%

Procedure

The title compound was prepared in a manner similar to the method of (1R,2S)-2-(3-iodo-1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-one using (1R,2S)-5′-fluoro-2-(1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-one (240 mg, 0.818 mmol). Purification using Biotage Isolera with SNAP 25 g column with 5-90% EtOAc in hexane yielded the title compound as a cream solid (195 mg, 57%; 97% e.e.) with the major (1R,2S) enantiomer eluting at 3.7 min (Phenomenex Lux 5μ Cellulose-2 (150×4.6 mm); isocratic 25% EtOH in n-hexane; 1.5 mL/min; 24° C.; Detection: 254 nm). From the racemic reference standard, the retention time of the (1S,2R) enantiomer was 3.2 min using this method. NMR (400 MHz, CD3OD) δ 7.47 (s, 1H), 7.38 (d, J=8.4 Hz, 1H), 7.01 (d, J=8.8 Hz, 1H), 6.88 (dd, J=8.8, 4.4 Hz, 1H), 6.79 (t, J=8.8 Hz, 1H), 5.69 (d, J=8.4 Hz, 1H), 3.38 (t, J=8.8 Hz, 1H), 2.28 (dd, J=8.8, 4.2 Hz, 1H), 2.21 (dd, J=9.2, 4.4 Hz, 1H); MS ESI 420.0 [M+H]+, calcd for [C17H11FIN3O+H]+ 420.0.

Workup

  1. customPurification

Sources & evidence

ORD record
ord-07ce732b40374195bc08ec0317cef424
Source dataset
uspto-grants-2014_12
Patent number
US08921545B2

Reaction notes

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