Diisopropylethylamine → N-(1,1-dimethylethyl)-2,4-difluoro-5-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]benzenesulfonamide

HRID 1992152Notes

Reaction equation

HRID 1992152 reaction equation
[CH3:1][C:2]([NH:5][S:6]([C:9]1[C:10]([F:19])=[CH:11][C:12]([F:18])=[C:13]([CH:17]=1)[C:14]([OH:16])=O)(=[O:8])=[O:7])([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.ClC1C(C([N:62]2[CH2:67][CH2:66][C:65]([C:88]3[CH:93]=[CH:92][CH:91]=[C:90]([F:94])[CH:89]=3)([CH2:68][CH2:69][N:70]3[CH:75]4[CH2:76][CH2:77][CH:71]3[CH2:72][CH:73]([N:78]3[C:82]5[CH:83]=[CH:84][CH:85]=[CH:86][C:81]=5[N:80]=[C:79]3[CH3:87])[CH2:74]4)[CH2:64][CH2:63]2)=O)=C(Cl)C=CC=1S(NC)(=O)=O>>[CH3:4][C:2]([NH:5][S:6]([C:9]1[CH:17]=[C:13]([C:14]([N:62]2[CH2:63][CH2:64][C:65]([C:88]3[CH:93]=[CH:92][CH:91]=[C:90]([F:94])[CH:89]=3)([CH2:68][CH2:69][N:70]3[CH:71]4[CH2:77][CH2:76][CH:75]3[CH2:74][CH:73]([N:78]3[C:82]5[CH:83]=[CH:84][CH:85]=[CH:86][C:81]=5[N:80]=[C:79]3[CH3:87])[CH2:72]4)[CH2:66][CH2:67]2)=[O:16])[C:12]([F:18])=[CH:11][C:10]=1[F:19])(=[O:7])=[O:8])([CH3:1])[CH3:3]

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167764165-{[(1,1-Dimethylethyl)amino]sulfonyl}-2,4-difluorobenzoic acidHCID 587277792,4-dichloro-3-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]-N-methylbenzenesulfonamide

Product 1

HCID 58727773N-(1,1-dimethylethyl)-2,4-difluoro-5-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]benzenesulfonamideYield 40%

Procedure

Prepared from a mixture of 5-{[(1,1-dimethylethyl)amino]sulfonyl}-2,4-difluorobenzoic acid 882-3b 1-(8-{2-[4-(3-fluorophenyl)-4-piperidinyl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole (100 mg, 0.16 mmol, 1 equiv), DIEA (117 μL, 0.66 mmol, 4 equiv) and HATU (62 mg, 0.16 mmol, 1 equiv) following the general procedure for 2,4-dichloro-3-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]-N-methylbenzenesulfonamide 1. The crude product was purified by column chromatography on silica gel eluting with 10% 2M NH3 in methanol in ethyl acetate to afford N-(1,1-dimethylethyl)-2,4-difluoro-5-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]benzenesulfonamide (example 882) as a white solid (46 mg, 40% yield).

Workup

  1. customThe crude product was purified by column chromatography on silica gel eluting with 10% 2M NH3 in methanol in ethyl acetate

Sources & evidence

ORD record
ord-04a9175b8b604359a5a4f185e4f4ba3d
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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