Diisopropylethylamine → HCID 59272930, compound

HRID 1510601Notes

Reaction equation

HRID 1510601 reaction equation
[NH2:1][C@@H:2]([CH3:37])[C@@H:3]([C:27]1[CH:36]=[CH:35][C:30]2[O:31][CH2:32][CH2:33][O:34][C:29]=2[CH:28]=1)[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=1)[C:17]([O:19][CH2:20][CH:21]([CH3:23])[CH3:22])=[O:18])[N:9]=[CH:8]2.[F:38][C:39]([F:44])([CH3:43])[C:40](O)=[O:41].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:38][C:39]([F:44])([CH3:43])[C:40]([NH:1][C@@H:2]([CH3:37])[C@@H:3]([C:27]1[CH:36]=[CH:35][C:30]2[O:31][CH2:32][CH2:33][O:34][C:29]=2[CH:28]=1)[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=1)[C:17]([O:19][CH2:20][CH:21]([CH3:22])[CH3:23])=[O:18])[N:9]=[CH:8]2)=[O:41]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27828252,2-Difluoropropionic acidHCID 59272916HCID 59272916, compound

Product 1

HCID 59272930HCID 59272930, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Isobutyl 3-(5-((1R,2S)-2-amino-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)propoxy)-1H-indazol-1-yl)benzoate (I4b) (0.5 g, 1.00 mmol), 2,2-difluoropropanoic acid (0.16 g, 1.45 mmol) and HBTU (0.567 g, 1.50 mmol) in DCM (4 mL) was treated with DIEA (0.696 mL, 3.99 mmol), the mixture was stirred at ambient temperature for 1 hour. The reaction was quenched by addition 10% NaHSO4 (aq), brine was added to help phase separation. The lower red DCM phase was separated, the waterphase was extracted with one portion of EtOAc, the combined organic solutions were dried over MgSO4 and filtered, solvents was removed by evaporation. Obtained a crude product as red oil. The crude material was further purified by flashchromatography using an 70 g prepacked silica column, an gradient of 0% to 50% EtOAc in Heptane was applied. Fractions with product was combined and solvents was removed by evaporation. An slightly yellow sticky oil was obtained after final evaporation from DCM. Yield 540 mg (91%).

Workup

  1. customThe reaction was quenched by addition 10% NaHSO4 (aq), brine
  2. additionwas added
  3. customphase separation
  4. customThe lower red DCM phase was separated
  5. extractionthe waterphase was extracted with one portion of EtOAc
  6. dry with materialthe combined organic solutions were dried over MgSO4
  7. filtrationfiltered
  8. customsolvents was removed by evaporation

Sources & evidence

ORD record
ord-61dee58357b74200b162635bd1108ce9
Source dataset
uspto-grants-2012_07
Patent number
US08211930B2

Reaction notes

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