4-{[(Tert-butoxy)carbonyl]amino}bicyclo[2.2.2]octane-1-carboxylic acid → tert-butyl 4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)-bicyclo[2.2.2]octan-1-ylcarbamate

HRID 1854305Notes

Reaction equation

HRID 1854305 reaction equation
ClC1C=C(S(NC23CCC(C4N5C6C=CN(S(C7C=CC(C)=CC=7)(=O)=O)C=6N=CC5=NN=4)(CC2)CC3)(=O)=O)C=CC=1.[NH:42]([C:44]1[N:45]=[C:46]2[CH:52]=[CH:51][N:50]([S:53]([C:56]3[CH:62]=[CH:61][C:59]([CH3:60])=[CH:58][CH:57]=3)(=[O:55])=[O:54])[C:47]2=[N:48][CH:49]=1)[NH2:43].[C:63]([O:67][C:68]([NH:70][C:71]12[CH2:78][CH2:77][C:74]([C:79](O)=[O:80])([CH2:75][CH2:76]1)[CH2:73][CH2:72]2)=[O:69])([CH3:66])([CH3:65])[CH3:64]>>[S:53]([N:50]1[C:47]2=[N:48][CH:49]=[C:44]([NH:42][NH:43][C:79]([C:74]34[CH2:75][CH2:76][C:71]([NH:70][C:68](=[O:69])[O:67][C:63]([CH3:65])([CH3:64])[CH3:66])([CH2:72][CH2:73]3)[CH2:78][CH2:77]4)=[O:80])[N:45]=[C:46]2[CH:52]=[CH:51]1)([C:56]1[CH:62]=[CH:61][C:59]([CH3:60])=[CH:58][CH:57]=1)(=[O:54])=[O:55]

Participants

4

Reactant 3

HCID 231507384-{[(Tert-butoxy)carbonyl]amino}bicyclo[2.2.2]octane-1-carboxylic acidHCID 580097923-chloro-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)benzenesulfonamideHCID 580098102-Hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 58009918tert-butyl 4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)-bicyclo[2.2.2]octan-1-ylcarbamate

Procedure

The precursor to Example #H.1.1, 3-chloro-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)benzenesulfonamide, was prepared as shown in Scheme B. 2-Hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (Preparation #9) and 4-(tert-butoxycarbonylamino)bicyclo-[2.2.2]octane-1-carboxylic acid are reacted following the conditions given in General Procedure A to give tert-butyl 4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)bicyclo[2.2.2]octan-1-ylcarbamate. This hydrazide is cyclized using the conditions given in General Procedure C to afford tert-butyl 4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-ylcarbamate. This carbamate is deprotected using General Procedure I to yield 4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-amine. This amine is sulfonylated using the conditions described in General Procedure N to give the precursor to Example #H.1.1. The reaction sequence detailed above is translated in the preparations and examples section to “using A from Preparation #9 and 4-(tert-butoxycarbonylamino)bicyclo-[2.2.2]octane-1-carboxylic acid [Prime Organics], C with TEA, I, N from 3-chlorobenzenesulfonyl chloride”.

Sources & evidence

ORD record
ord-92384b07d0f34ba8a1e69ae213f8f901
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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