Serinol → HCID 70976540, compound

HRID 882283Notes

Reaction equation

HRID 882283 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2].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.[NH2:64][CH:65]([CH2:68][OH:69])[CH2:66][OH:67]>CN(C=O)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[CH:16][C:17]([C:18]([NH:64][CH:65]([CH2:68][OH:69])[CH2:66][OH:67])=[O:20])=[CH:21][CH:22]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 68294SerinolHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70976494HCID 70976494, compound

Product 1

HCID 70976540HCID 70976540, compoundYield 20.55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a flask charged with 4-((2S,4R)-1-acetyl-2-methyl-4-(pyridin-2-ylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (for a preparation see Intermediate 23) (70 mg, 0.174 mmol) and HATU (80 mg, 0.209 mmol) was added DMF (3 mL) and the resulting solution was treated with DIPEA (0.091 mL, 0.523 mmol) and after 5 min by 2-aminopropane-1,3-diol (31.8 mg, 0.349 mmol). The reaction was concentrated in vacuo, residue partitioned between water and EtOAc. the phases were separated and the aqueous extracted with EtOAc (×2). The combined organic layers were washed with saturated NaHCO3 (3×) then brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by MDAP (HpH) and the residue triturated with Et2O to give 4-((2S,4R)-1-acetyl-2-methyl-4-(pyridin-2-ylamino)-1,2,3,4-tetrahydroquinolin-6-yl)-N-(1,3-dihydroxypropan-2-yl)benzamide (17 mg, 0.036 mmol, 20.55% yield) as a very pale yellow solid. LCMS (HpH, 2 min), Rt=0.74 min, MH+=475.

Workup

  1. concentrationThe reaction was concentrated in vacuo, residue
  2. custompartitioned between water and EtOAc
  3. customthe phases were separated
  4. extractionthe aqueous extracted with EtOAc (×2)
  5. washThe combined organic layers were washed with saturated NaHCO3 (3×)
  6. dry with materialbrine, dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by MDAP (HpH)
  9. customthe residue triturated with Et2O

Sources & evidence

ORD record
ord-cf33d60bbcab4f11a00ed7eaaefb1fb7
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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