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Diisopropylethylamine → HCID 178422437, compound

HRID 216516
Notes
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Reaction equation

HRID 216516 reaction equation
[F:1][C:2]1[C:7]2[NH:8][CH:9]=[N:10][C:6]=2[CH:5]=[C:4]([C:11]([OH:13])=O)[C:3]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[CH3:22].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=[CH:53][CH:54]=[CH:55][C:50]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.C1([N:69](C)[OH:70])CC1>C1COCC1.C(Cl)Cl>[CH:54]1([CH2:53][O:70][NH:69][C:11]([C:4]2[C:3]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=3[CH3:22])=[C:2]([F:1])[C:7]3[NH:8][CH:9]=[N:10][C:6]=3[CH:5]=2)=[O:13])[CH2:55][CH2:50]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 21114231Cyclopropyl methyl hydroxylamine hydrochlorideHCID 178422438HCID 178422438, compound

Product 1

HCID 178422437HCID 178422437, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 6344
Dichloromethane
Solvent
HCID 8028TetrahydrofuranSolvent

Procedure

7-Fluoro-6-(4-bromo-2-methyl-phenylamino)-1H-benzoimidazole-5-carboxylic acid 10a (48 mg, 0.132 mmol) is dissolved in 1:1 THF: methylene chloride (1 mL) and Hunig's base (0.23 μL, 1.32 mmol) is added followed by PyBOP (82 mg, 0.158 mmol). After a few minutes, cyclopropyl methyl hydroxylamine hydrochloride (20 mg, 0.158 mmol) (WO 00/42022) is added. After the reaction is complete, the mixture is partitioned between methylene chloride and saturated NaHCO3 solution. The layers are separated and the organic layer is washed with saturated NaHCO3 and brine. The organic layer is dried (Na2SO4) and concentrated under reduced pressure. After purification by FCC (elute with 20:1 methylene chloride/MeOH), 25 mg (45%) of pure desired product is isolated: MS ESI (+) m/z 435, 433 (M+1 Br pattern) detected; MS ESI (−) m/z 433, 431 (M−1 Br pattern) detected; 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 8.02 (s, 1H), 7.28 (s, 1H), 7.43 (d, 1H), 7.07 (dd, 1H), 6.36 (m, 1H), 3.70 (d, 2H), 2.38 (s, 3H), 0.86 (m, 1H), 0.41 (m, 2H), 0.13 (m, 2H); 19F NMR (376 MHz, CDCl3) −134.05 (s).

Workup

  1. waitAfter a few minutes
  2. customthe mixture is partitioned between methylene chloride and saturated NaHCO3 solution
  3. customThe layers are separated
  4. washthe organic layer is washed with saturated NaHCO3 and brine
  5. dry with materialThe organic layer is dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification
  8. washby FCC (elute with 20:1 methylene chloride/MeOH)

Sources & evidence

ORD record
ord-cd59ac85729f44f2ae9a16ef38584918
Source dataset
uspto-grants-2012_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08193230B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes