1-Methylcyclopropanecarboxylic acid → N-((1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-yl)-1-methylcyclopropanecarboxamide

HRID 13153

Reaction equation

HRID 13153 reaction equation
[CH3:1][C:2]1([C:5]([OH:7])=O)[CH2:4][CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[O:41]1[CH2:46][CH2:45][O:44][C:43]2[CH:47]=[C:48]([C@@H:51]([O:55][C:56]3[CH:57]=[C:58]4[C:62](=[CH:63][CH:64]=3)[N:61]([C:65]3[CH:70]=[CH:69][C:68]([F:71])=[CH:67][CH:66]=3)[N:60]=[CH:59]4)[C@@H:52]([NH2:54])[CH3:53])[CH:49]=[CH:50][C:42]1=2>CN1C(=O)CCC1.O>[O:41]1[CH2:46][CH2:45][O:44][C:43]2[CH:47]=[C:48]([C@@H:51]([O:55][C:56]3[CH:57]=[C:58]4[C:62](=[CH:63][CH:64]=3)[N:61]([C:65]3[CH:66]=[CH:67][C:68]([F:71])=[CH:69][CH:70]=3)[N:60]=[CH:59]4)[C@@H:52]([NH:54][C:5]([C:2]3([CH3:1])[CH2:4][CH2:3]3)=[O:7])[CH3:53])[CH:49]=[CH:50][C:42]1=2

Participants

7

Reactant 4

HCID 813261-Methylcyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59339888(1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine

Product 1

HCID 59339637N-((1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-yl)-1-methylcyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

1-methylcyclopropanecarboxylic acid (39 mg, 0.39 mmol), HATU (150 mg, 0.39 mmol) and DIPEA (170 μl, 0.97 mmol) in NMP (2 mL) was stirred at r.t. for 5 min until a solution had formed. To this solution was added (1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine (19a) (102 mg, 0.24 mmol) dissolved in NMP (1 mL). The reaction mixture was stirred for 2 h at r.t. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2×10 mL), the organic phases was then washed with brine, dried over Na2SO4, filtered and evaporated. The remaining oily residue was purified by HPLC. Fractions containing product was freezedried. Yield 68 mg (55%10).

Workup

  1. customhad formed
  2. extractionextracted with EtOAc (2×10 mL)
  3. washthe organic phases was then washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe remaining oily residue was purified by HPLC
  8. additionFractions containing product
  9. customwas freezedried

Sources & evidence

ORD record
ord-a43fb47ffcda4c3a89b6f9d1af0600af
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Linked notes

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