D-Lactic Acid → HCID 86690698, compound

HRID 711372Notes

Reaction equation

HRID 711372 reaction equation
Cl.[Cl:2][C:3]1[CH:12]=[CH:11][C:10]2[N:9]=[CH:8][C:7]3[N:13]=[N:14][N:15]([CH:16]4[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]4)[C:6]=3[C:5]=2[N:4]=1.[OH:22][C@H:23]([CH3:27])[C:24](O)=[O:25].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>CN(C=O)C.O>[Cl:2][C:3]1[CH:12]=[CH:11][C:10]2[N:9]=[CH:8][C:7]3[N:13]=[N:14][N:15]([CH:16]4[CH2:21][CH2:20][N:19]([C:24](=[O:25])[C@H:23]([OH:22])[CH3:27])[CH2:18][CH2:17]4)[C:6]=3[C:5]=2[N:4]=1

Participants

7

Reactant 4

HCID 61503D-Lactic AcidHCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 86690695HCID 86690695, compound

Product 1

HCID 86690698HCID 86690698, compoundYield 20.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 8-chloro-1-(piperidin-4-yl)-1H-[1,2,3]triazolo[4,5-c][1,5]naphthyridine hydrochloride (600 mg, 1.85 mmol) in DMF (15 mL) was added (R)-2-hydroxypropanoic acid (540 mg, 1.85 mmol), HATU (850 mg, 2.21 mmol) and DIEA (0.8 mL, 3.70 mmol). The mixture was stirred at room temperature overnight. Another 3 eq of HATU and 2 eq of DIEA were added because the reaction did not go to completion as shown by HPLC-MS. The mixture was stirred for another 30 min, and was then diluted with water. The resulting mixture was extracted with ethyl acetate twice. The combined organic layers were dried over anhydrous Na2SO4, and concentrated to give the crude product, which was subsequently purified by chromatography on silica gel using EtOAc:PE as eluent to afford (R)-1-(4-(8-chloro-1H-[1,2,3]triazolo[4,5-c][1,5]naphthyridin-1-yl)piperidin-1-yl)-2-hydroxypropan-1-one as a yellow solid (136 mg, yield 20.4%). MS (m/z): 361 (M+H)+.

Workup

  1. stirringThe mixture was stirred for another 30 min
  2. extractionThe resulting mixture was extracted with ethyl acetate twice
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas subsequently purified by chromatography on silica gel

Sources & evidence

ORD record
ord-f99a76068a65418c92e887d374cc3944
Source dataset
uspto-grants-2015_11
Patent number
US09181264B2

Reaction notes

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