Diisopropylethylamine → 4-fluoro-7-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenyl-1-piperidinyl)carbonyl]-1,3-benzoxazol-2(3H)-one

HRID 1992158Notes

Reaction equation

HRID 1992158 reaction equation
[F:1][C:2]1[C:7]2[NH:8][C:9](=[O:11])[O:10][C:6]=2[C:5]([C:12]([OH:14])=O)=[CH:4][CH:3]=1.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:57]2[CH2:62][CH2:61][C:60]([C:83]3[CH:88]=[CH:87][CH:86]=[C:85](F)[CH:84]=3)([CH2:63][CH2:64][N:65]3[CH:70]4[CH2:71][CH2:72][CH:66]3[CH2:67][CH:68]([N:73]3[C:77]5[CH:78]=[CH:79][CH:80]=[CH:81][C:76]=5[N:75]=[C:74]3[CH3:82])[CH2:69]4)[CH2:59][CH2:58]2)=O)=C(Cl)C=CC=1S(NC)(=O)=O>>[F:1][C:2]1[C:7]2[NH:8][C:9](=[O:11])[O:10][C:6]=2[C:5]([C:12]([N:57]2[CH2:58][CH2:59][C:60]([CH2:63][CH2:64][N:65]3[CH:66]4[CH2:72][CH2:71][CH:70]3[CH2:69][CH:68]([N:73]3[C:77]5[CH:78]=[CH:79][CH:80]=[CH:81][C:76]=5[N:75]=[C:74]3[CH3:82])[CH2:67]4)([C:83]3[CH:84]=[CH:85][CH:86]=[CH:87][CH:88]=3)[CH2:61][CH2:62]2)=[O:14])=[CH:4][CH:3]=1

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 146906864-Fluoro-2-oxo-2,3-dihydro-1,3-benzoxazole-7-carboxylic 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 587284034-fluoro-7-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenyl-1-piperidinyl)carbonyl]-1,3-benzoxazol-2(3H)-oneYield 17%

Procedure

Prepared from a mixture of 4-fluoro-2-oxo-2,3-dihydro-1,3-benzoxazole-7-carboxylic acid (9.8 mg, 0.05 mmol, 1 equiv), endo 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride (25 mg, 0.05 mmol, 1 equiv), DIEA (36 μL, 0.2 mmol, 4 equiv) and HATU (19 mg, 0.05 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 (example 880). The crude product was purified by prep HPLC (HPLC Method C) to provide 4-fluoro-7-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenyl-1-piperidinyl)carbonyl]-1,3-benzoxazol-2(3H)-one as a white solid (5 mg, 17% yield).

Workup

  1. customThe crude product was purified by prep HPLC (HPLC Method C)

Sources & evidence

ORD record
ord-3eea75def15a4fd18eda654ce7edff84
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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