Carbon Dioxide → HCID 56654139, compound

HRID 1409512Notes

Reaction equation

F[C:2](F)(F)C(O)=O.Cl[C:9]1[N:14]=[C:13]([F:15])[C:12]2[O:16][C:17]3[C:22]([C:23]4([C:27]5[CH:28]=N[CH:30]=[CH:31][C:26]=5[C:25]([NH2:32])=[N:24]4)[C:11]=2[CH:10]=1)=[CH:21][C:20]([C:33]1[C:34]([F:39])=[N:35][CH:36]=[CH:37][CH:38]=1)=[CH:19][CH:18]=3.FC(F)(F)C(O)=O.[F:47][C:48]1[C:53]2[O:54][C:55]3[C:60]([C:61]4([C:65]5[CH:66]=[N:67][CH:68]=[CH:69][C:64]=5[C:63]([NH2:70])=[N:62]4)[C:52]=2[CH:51]=[C:50]([C:78]2[CH:83]=[CH:82][N:81]=[C:80]([F:84])[CH:79]=2)[N:49]=1)=[CH:59][C:58]([C:71]1[C:72]([F:77])=[N:73][CH:74]=[CH:75][CH:76]=1)=[CH:57][CH:56]=3.C(=O)=O>>[F:47][C:48]1[C:53]2[O:54][C:55]3[C:60]([C:61]4([C:65]5[CH:66]=[N:67][CH:68]=[CH:69][C:64]=5[C:63]([NH2:70])=[N:62]4)[C:52]=2[CH:51]=[C:50]([C:78]2[CH:83]=[CH:82][N:81]=[C:80]([F:84])[CH:79]=2)[N:49]=1)=[CH:59][C:58]([C:71]1[C:72]([F:77])=[N:73][CH:74]=[CH:75][CH:76]=1)=[CH:57][CH:56]=3.[O:54]1[CH2:55][CH2:60][CH:61]=[C:52]([C:9]2[N:14]=[C:13]([F:15])[C:12]3[O:16][C:17]4[C:22]([C@@:23]5([C:27]6[C:26](=[CH:31][CH:30]=[CH:2][CH:28]=6)[C:25]([NH2:32])=[N:24]5)[C:11]=3[CH:10]=2)=[CH:21][C:20]([C:33]2[C:34]([F:39])=[N:35][CH:36]=[CH:37][CH:38]=2)=[CH:19][CH:18]=4)[CH2:53]1

Participants

Reactant 3

HCID 280Carbon Dioxide

HCID 89653834HCID 89653834, compound

HCID 89653917HCID 89653917, compound

Product 2

HCID 56654139HCID 56654139, compound

HCID 66728324HCID 66728324, compound

Procedure

The titled compound was synthesized by procedures and steps analogous to those described in Example 5 above, but using 3-chloro-1-fluoro-7-(2-fluoropyridin-3-yl)spiro[chromeno[2,3-c]pyridine-5,3′-pyrrolo[3,4-c]pyridin]-1′-amine 2,2,2-trifluoroacetate (14d) and in step 4. 1-Fluoro-7-(2-fluoropyridin-3-yl)-3-(2-fluoropyridin-4-yl)spiro[chromeno[2,3-c]pyridine-5,3′-pyrrolo[3,4-c]pyridin]-1′-amine 2,2,2-trifluoroacetate (14e, 77 mg) was subjected to chromatography using supercritical CO2 (additives 26% MeOH with 20 mM NH3) on a Chrialcel ADH column (21×250 mm, 5 μm) eluting at a flow rate 65 ml/min (100 bar pressure, 40° C. column temperature). The first peak (retention time=5.3 min) provided (S)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-7-(2-fluoropyridin-3-yl)spiro[chromeno[2,3-c]pyridine-5,1′-isoindol]-3′-amine (Example 14-A; >99% ee), and the second peak (retention time=7.0 min) provided (R)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-7-(2-fluoropyridin-3-yl)spiro[chromeno[2,3-c]pyridine-5,1′-isoindol]-3′-amine (Example 14-B; TFA salt; >99% ee).

Workup

washeluting at a flow rate 65 ml/min (100 bar pressure, 40° C. column temperature)

Sources & evidence

ORD record: ord-56f9ce3a72d44a51932d21a0a9dcb163
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921363B2

Reaction notes

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