Hydrochloric Acid → HCID 44515373, compound

HRID 1098989Notes

Reaction equation

HRID 1098989 reaction equation
[O:1]1[C:5]2[CH:6]=[C:7]([C@@H:10]([O:14][C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[N:20]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[N:19]=[CH:18]4)[C@@H:11]([NH2:13])[CH3:12])[CH:8]=[CH:9][C:4]=2[CH2:3][CH2:2]1.[F:31][C:32]([F:37])([CH3:36])[C:33](O)=[O:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.Cl>CN1C(=O)CCC1>[O:1]1[C:5]2[CH:6]=[C:7]([C@@H:10]([O:14][C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[N:20]([C:24]3[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=3)[N:19]=[CH:18]4)[C@@H:11]([NH:13][C:33](=[O:34])[C:32]([F:37])([F:31])[CH3:36])[CH3:12])[CH:8]=[CH:9][C:4]=2[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27828252,2-Difluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59339828(1R,2S)-1-(2,3-dihydrobenzofuran-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine

Product 1

HCID 44515373HCID 44515373, compoundYield 62.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

To a solution of (1R,2S)-1-(2,3-dihydrobenzofuran-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine (306a, 85 mg, 0.21 mmol) in NMP (1 mL) was added a solution of 2,2-difluoropropanoic acid (37 mg, 0.34 mmol), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.128 g, 340 nmol), and N-ethyl-N-isopropylpropan-2-amine (140 μL, 840 μmol) in NMP (2 mL). The mixture was stirred at r.t. for 2 h. Then aq. HCl (1N, 30 mL) was added, and the mixture was extracted with ethyl acetate (3×45 ml). The organic phase was dried and purified by flash chromatography on silica gel with ethyl acetane/n-heptane (2:1) to give 65 mg (62%) of the title compound.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×45 ml)
  2. customThe organic phase was dried
  3. custompurified by flash chromatography on silica gel with ethyl acetane/n-heptane (2:1)

Sources & evidence

ORD record
ord-d5bedf30fb734ef49184d27af00bb13b
Source dataset
uspto-grants-2012_03
Patent number
US08143290B2

Reaction notes

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