Dichloromethane → HCID 57826752, compound

HRID 1961084Notes

Reaction equation

HRID 1961084 reaction equation
C[C:2]1[CH:3]=[C:4]([C:13](OC)=[O:14])[S:5][C:6]=1C1N(C)N=CC=1.[NH2:17][C@@H:18]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[C:38]([F:41])([F:40])[F:39])[CH2:19][N:20]1[C:28](=[O:29])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]1=[O:30].C([N:45]([CH:48]([CH3:50])[CH3:49])[CH2:46]C)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)[N:60]1CCC[CH2:61]1.[CH2:75](Cl)Cl>>[CH3:46][N:45]1[C:48]([C:49]2[CH:3]=[C:4]([C:13]([NH:17][C@@H:18]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[C:38]([F:41])([F:39])[F:40])[CH2:19][N:20]3[C:28](=[O:29])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:21]3=[O:30])=[O:14])[S:5][C:6]=2[CH3:2])=[C:50]([CH3:75])[CH:61]=[N:60]1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 57826760HCID 57826760, compoundHCID 578268082-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione

Product 1

HCID 57826752HCID 57826752, compoundYield 71.7%

Conditions

Temperature
25 °C

Procedure

To a solution of methyl 4-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (217 mg, 0.918 mmol), 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (353 mg, 0.92 mmol)[prepared according to Preparation 6] and diisopropylethylamine (0.800 ml, 4.59 mmol) in DCM at 25° C. was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (472 mg, 1.01 mmol) in one portion. The solution stirred at 25° C. for 12 h and was then partitioned between H2O-DCM. The aqueous phase was washed several times with DCM and the combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 30-70% EtOAc in hexanes) yielding 4-(1,4-dimethyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-methyl-2-thiophenecarboxamide (373 mg, 0.66 mmol, 71.7% yield) as a yellow foam: LCMS (ES) m/e 567 (M+H)+.

Workup

  1. customwas then partitioned between H2O-DCM
  2. washThe aqueous phase was washed several times with DCM
  3. dry with materialthe combined organic fractions were dried over Na2SO4
  4. concentrationconcentrated
  5. custompurified via column chromatography (silica, 30-70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0b66ff5623fb4dccbe466dfc1f66b3cf
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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