1,2-Dichloroethane → 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-((S)-2,3-dihydroxypropyl)benzamide

HRID 882278Notes

Reaction equation

HRID 882278 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](O)=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.C(N1CCOCC1)C.[NH2:56][CH2:57][C@H:58]([OH:61])[CH2:59][OH:60].C1C=CC2N(O)N=NC=2C=1>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:56][CH2:57][C@H:58]([OH:61])[CH2:59][OH:60])=[O:19])=[CH:21][CH:22]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2]

Participants

8

Reactant 6

HCID 111,2-Dichloroethane2×HCID 7525Ethylmorpholine2×HCID 757711-HydroxybenzotriazoleHCID 4409023-Amino-1,2-propanediol, (S)-2×HCID 22729017HOBT hydrochlorideHCID 709764624-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid

Product 1

HCID 714674634-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-((S)-2,3-dihydroxypropyl)benzamideYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (for a preparation see Intermediate 4) (90 mg, 0.211 mmol) in DMF (2 mL) was treated with EDC (48.5 mg, 0.253 mmol), HOBT hydrochloride (38.8 mg, 0.253 mmol) and N-ethylmorpholine (0.080 mL, 0.633 mmol) and after 3 min with (S)-3-aminopropane-1,2-diol (38.5 mg, 0.422 mmol). The resulting mixture was stirred at room temperature for 5 h then EDC (48.5 mg, 0.253 mmol), N-ethyl morpholine (0.080 mL, 0.633 mmol), HOBT (38.8 mg, 0.253 mmol) and further (S)-3-aminopropane-1,2-diol (38.5 mg, 0.422 mmol) were added and the corresponding mixture was stirred for 16 h then concentrated in vacuo. The residue was partitioned between water and EtOAc and the layers were separated. The aqueous phase was extracted with EtOAc (×2) and the combined organic layers were washed with saturated aqueous NaHCO3 (×3), then brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by MDAP to give 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N—((S)-2,3-dihydroxypropyl)benzamide (30 mg, 29%) as a white solid. LCMS (HpH, 2 min), Rt=0.75 min, MH+=500.

Workup

  1. stirringthe corresponding mixture was stirred for 16 h
  2. concentrationthen concentrated in vacuo
  3. customThe residue was partitioned between water and EtOAc
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted with EtOAc (×2)
  6. washthe combined organic layers were washed with saturated aqueous NaHCO3 (×3)
  7. dry with materialbrine, dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by MDAP

Sources & evidence

ORD record
ord-efc63f160e5c4b93aa7f8c5139a4eacc
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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