Diisopropylethylamine → HCID 78035251, compound

HRID 1422591Notes

Reaction equation

HRID 1422591 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.[NH2:44][C:45]1[CH:46]=[CH:47][C:48]([F:67])=[C:49]([C:51]23[CH2:58][CH:57]2[CH2:56][CH2:55][S:54][C:53]([NH:59][C:60](=[O:66])[O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[N:52]3)[CH:50]=1>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:44][C:45]2[CH:46]=[CH:47][C:48]([F:67])=[C:49]([C:51]34[CH2:58][CH:57]3[CH2:56][CH2:55][S:54][C:53]([NH:59][C:60](=[O:66])[O:61][C:62]([CH3:63])([CH3:65])[CH3:64])=[N:52]4)[CH:50]=2)=[O:10])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27628725-Chloro-2-picolinic acidHCID 86675578HCID 86675578, compoundHCID 178484293HCID 178484293, compound

Product 1

HCID 78035251HCID 78035251, compoundYield 39.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

Commercially available 5-chloro-2-pyridinecarboxylic acid (30 mg, 0.19 mmol) was dissolved in dichloromethane (3 ml) and DMF (1 ml), then diisopropylethylamine (85 μl, 0.50 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate (HATU) (87 mg, 0.23 mmol) were added at 23° C. After 15 min of stiffing tert-butyl (1SR,7SR)-1-(5-amino-2-fluorophenyl)-4-thia-2-azabicyclo[5.1.0]oct-2-en-3-ylcarbamate (intermediate rac-A8a) (53 mg, 0.15 mmol) was added. The brown solution was stirred for 20 hours at 23° C. The grey reaction mixture was poured on ice cold sat. NaHCO3 solution and extracted twice with dichloromethane. The organic layers were washed with brine, dried over Na2SO4, filtered and evaporated to give a brown oil which was chromatographed on 5 g silica gel with cyclohexane/ethyl acetate 1:1 to give the tert-butyl (1SR,7SR)-1-(5-(5-chloropicolinamido)-2-fluorophenyl)-4-thia-2-azabicyclo[5.1.0]oct-2-en-3-ylcarbamate (29 mg; 31%) as a light yellow oil. MS (ISP): m/z=491.1 [(M+H)+] and 493.2 [(M+2+H)+].

Workup

  1. additionThe grey reaction mixture was poured on ice cold sat. NaHCO3 solution
  2. extractionextracted twice with dichloromethane
  3. washThe organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give a brown oil which
  8. customwas chromatographed on 5 g silica gel with cyclohexane/ethyl acetate 1:1

Sources & evidence

ORD record
ord-3e92effc74db43fea5ac9a476ca2b1bf
Source dataset
uspto-grants-2015_01
Patent number
US08927535B2

Reaction notes

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