1,2-Dichloroethane → 3-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-(3-chloro-7-azaindol-5-ylmethylaminocarbonylmethyl)pyrazinone

HRID 398395Notes

Reaction equation

HRID 398395 reaction equation
[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:10]([NH:11][C:12]3[C:13](=[O:23])[N:14]([CH2:19][C:20]([OH:22])=O)[C:15]([Cl:18])=[CH:16][N:17]=3)[CH2:9][O:8][CH2:7]2)[CH2:3][CH2:2]1.Cl.Cl.[NH2:26][CH2:27][C:28]1[CH:29]=[C:30]2[C:34](=[N:35][CH:36]=1)[NH:33][CH:32]=[C:31]2[Cl:37].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl.CO>CN(C=O)C.Cl>[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:10]([NH:11][C:12]3[C:13](=[O:23])[N:14]([CH2:19][C:20]([NH:26][CH2:27][C:28]4[CH:29]=[C:30]5[C:34](=[N:35][CH:36]=4)[NH:33][CH:32]=[C:31]5[Cl:37])=[O:22])[C:15]([Cl:18])=[CH:16][N:17]=3)[CH2:9][O:8][CH2:7]2)[CH2:2][CH2:3]1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 887MethanolHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 230002415-Aminomethyl-3-chloro-7-azaindole bis-hydrochloride saltHCID 700236133-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-carboxymethylpyrazinone

Product 1

HCID 700233993-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-(3-chloro-7-azaindol-5-ylmethylaminocarbonylmethyl)pyrazinone

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-(trans-3-cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-carboxymethylpyrazinone from step 7 above (50 mg, 0.15 mmol) in DMF (1.0 mL) was added 5-aminomethyl-3-chloro-7-azaindole bis-hydrochloride salt (41 mg, 0.16 mmol) and HOBT (24 mg, 0.16 mmol). The solution was brought to pH 7 by the addition of DIEA (approximately 0.1 mL). EDC (70 mg, 0.24 mmol) was added and the solution was stirred at ambient temperature for 18 h. The reaction was concentrated in vacuo and partitioned between water and EtOAc. The organic phase was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography using 9:1 CH2Cl2:MeOH as eluant. The free base of the title compound was dissolved in MeOH containing 3 equivalents of aqueous HCl and the solution was evaporated in vacuo to give the HCl salt of the title compound as an amorphous solid (45 mg, TLC Rf=0.46, 92:8:0.4 CH2Cl2:MeOH:NH4OH; HPLC RT=8.6 min, method A; M+1 peak at m/z=508, electrospray mass spec).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. custompartitioned between water and EtOAc
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-9b8a72e5e81c41d9912a51af8d36b2f7
Source dataset
uspto-grants-2003_08
Patent number
US06610692B1

Reaction notes

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