Trifluoroacetic acid → HCID 23401111, compound

HRID 1063430Notes

Reaction equation

HRID 1063430 reaction equation
CC(O[C:6]([NH:8][C@H:9]([C:16]([OH:18])=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])(C)C.[CH:19]1(O)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.C1CC[CH:29]([N:32]=C=NC2CCCCC2)[CH2:28]C1.FC(F)(F)C(O)=O.C(CC(O)=O)#N.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C1C=CN=CC=1)C>[CH:19]1([O:18][C:16](=[O:17])[CH:9]([NH:8][C:6](=[O:7])[CH2:28][C:29]#[N:32])[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 7966CyclohexanolHCID 9740Cyanoacetic acidHCID 10868DicyclohexylcarbodiimideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11010409(2S)-2-(((tert-butoxy)carbonyl)amino)-2-phenylacetic acid

Product 1

HCID 23401111HCID 23401111, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Boc-L-α-phenylglycine (Va) and cyclohexanol were reacted in dichloromethane in the presence of DCC and catalytic amount of DMAP to give VIa (R=Boc) in almost quantitative yield. Treatment of VIa with trifluoroacetic acid yielded VIIa (R=H, Scheme 1) in 98% yield. VIIa was then coupled to alphacyanoacetic acid (VIII) using HATU as the coupling ERAB OR HADH2 inhibiting agent to afford (2-Cyano-acetylamino)-phenyl-acetic acid cyclohexyl ester (IXa). The reaction of IXa with triethyl orthoformate in acetic anhydride and catalytic anhydrous ZnCl2 at 130° C. gave an intermediate which upon reaction with hydrazine in 1,4-dioxane at 105° C. affords Xa in 51% yield. The [(5-Amino-1H-pyrazole-4-carbonyl)-amino]-phenyl-acetic acid cyclohexyl ester (Xa) was then treated with formamide at 145° C. to give the desired cyclized product (XIa). XIa was treated with Lawesson's reagent under inert gas atmosphere to afford XIIa. Hydrolysis of XIIa afforded the carboxylic acid XIVa, which was then coupled to hexamethyeneimine using the coupling reagent HATU to afford 1-Azepan-1-yl-2-phenyl-2-(4-thioxo-1,4-dihydro-1,4-dihrdropyrazolo[3,4-d]pyrimidin-5-yl)-ethanone (XVIa). Synthesis of Compounds of the Formula XVII and XVIII as Shown in Scheme 2: Description of Generic Scheme 2:

Workup

  1. customto give VIa (R=Boc) in almost quantitative yield

Sources & evidence

ORD record
ord-e367040e492449d9b2ba9b9d207caccf
Source dataset
uspto-grants-2005_11
Patent number
US06964957B2

Reaction notes

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