1,2-Dichloroethane → HCID 70976659, compound

HRID 882282Notes

Reaction equation

HRID 882282 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][CH:27]=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N1CCOCC1)C.[NH2:53][CH2:54][C@H:55]([OH:58])[CH2:56][OH:57]>CN(C=O)C.CCOCC>[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]([NH:53][CH2:54][C@H:55]([OH:58])[CH2:56][OH:57])=[O:19])=[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]

Participants

8

Reactant 5

HCID 111,2-Dichloroethane2×HCID 7525Ethylmorpholine2×HCID 757711-Hydroxybenzotriazole2×HCID 4409023-Amino-1,2-propanediol, (S)-2×HCID 70976494HCID 70976494, compound

Product 1

HCID 70976659HCID 70976659, compoundYield 43.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 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) in DMF (2 mL) was treated with EDC (40.1 mg, 0.209 mmol), HOBT (32.0 mg, 0.209 mmol) and N-ethylmorpholine (0.066 mL, 0.523 mmol) and after 3 min with (S)-3-aminopropane-1,2-diol (15.89 mg, 0.174 mmol). The resulting mixture was stirred at room temperature for 5 h then further EDC (40.1 mg, 0.209 mmol), N-ethylmorpholine (0.066 mL, 0.523 mmol), HOBT (32.0 mg, 0.209 mmol) and (S)-3-aminopropane-1,2-diol (15.89 mg, 0.174 mmol) were added and the mixture stirred for 16 h before concentrating in vacuo. The residue was partitioned between water and EtOAc and the layers were separated. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with saturated aqueous NaHCO3 (×3) then brine, dried over MgSO4 and concentrated in vacuo. Trituration of the residue with Et2O gave 4-((2S,4R)-1-acetyl-2-methyl-4-(pyridin-2-ylamino)-1,2,3,4-tetrahydroquinolin-6-yl)-N—((S)-2,3-dihydroxypropyl)benzamide (36 mg, 0.076 mmol, 43.5% yield) as a pale yellow solid.

Workup

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

Sources & evidence

ORD record
ord-1d0d053d411d416ebb393100cc45af13
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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