Hydrochloric Acid → HCID 44629311, compound

HRID 2088512Notes

Reaction equation

HRID 2088512 reaction equation
[C:1](=O)([O:27]C1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][C@@H:4]([N:8]1[CH:13]=[C:12]([Cl:14])[N:11]=[C:10]([NH:15][C:16]2[C:17]([CH3:25])=[N:18][C:19]([O:23][CH3:24])=[C:20]([CH3:22])[CH:21]=2)[C:9]1=[O:26])[CH:5]1[CH2:7][CH2:6]1.[CH2:38]([O:40][C:41]1[N:46]=[C:45]([CH3:47])[C:44]([NH2:48])=[CH:43][C:42]=1[CH3:49])[CH3:39].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.Cl>C1COCC1>[CH2:38]([O:40][C:41]1[N:46]=[C:45]([CH3:47])[C:44]([NH:48][C:1](=[O:27])[O:2][CH2:3][C@@H:4]([N:8]2[CH:13]=[C:12]([Cl:14])[N:11]=[C:10]([NH:15][C:16]3[C:17]([CH3:25])=[N:18][C:19]([O:23][CH3:24])=[C:20]([CH3:22])[CH:21]=3)[C:9]2=[O:26])[CH:5]2[CH2:7][CH2:6]2)=[CH:43][C:42]=1[CH3:49])[CH3:39]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 67117563HCID 67117563, compoundHCID 67159876HCID 67159876, compound

Product 1

HCID 44629311HCID 44629311, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-2-(5-chloro-3-(6-methoxy-2,5-dimethylpyridin-3-ylamino)-2-oxopyrazin-1(2H)-yl)-2-cyclopropylethyl 4-nitrophenyl carbonate (30 mg, 0.057 mmol) from Part A, 6-ethoxy-2,5-dimethylpyridin-3-amine (17 mg, 0.100 mmol), HOBt (9 mg, 0.063 mmol) and 4 Å molecular sieves (60 mg) in THF (1 mL) at room temperature was added triethylamine (23 μL, 0.17 mmol). The reaction mixture was stirred at room temperature for 48 h. The mixture was transferred to a separatory funnel containing 1 N HCl (5 mL) and the aqueous layer was extracted with EtOAc (3×10 ml). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by HPLC (MeCN/H2O with 0.1% TFA, C18 column) to afford (S)-2-(5-chloro-3-(6-methoxy-2,5-dimethylpyridin-3-ylamino)-2-oxopyrazin-1(2H)-yl)-2-cyclopropylethyl 6-ethoxy-2,5-dimethylpyridin-3-ylcarbamate (10 mg, 32% yield) as a yellow amorphous solid: 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.92 (s, 1H), 7.44 (s, 1H), 6.80 (s, 1H), 6.13 (s, 1H), 4.61-4.58 (m, 1H), 4.43 (dd, JAB=11.6, JAX=7.5 Hz, 1H), 4.31 (q, J=6.8 Hz, 2H), 4.26-4.21 (m, 1H), 3.92 (s, 3H), 2.41 (s, 3H), 2.29 (s, 3H), 2.17 (s, 3H), 2.10 (s, 3H), 1.33 (t, J=7.0 Hz, 3H), 1.25-1.19 (m, 1H), 0.88-0.81 (m, 1H), 0.65-0.55 (m, 2H), 0.38-0.34 (m, 1H); HRMS (ESI) m/e 557.2269 [(M+H)+, calcd for C27H34N6O5Cl 557.2279].

Workup

  1. customThe mixture was transferred to a separatory funnel
  2. extractionthe aqueous layer was extracted with EtOAc (3×10 ml)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by HPLC (MeCN/H2O with 0.1% TFA, C18 column)

Sources & evidence

ORD record
ord-0fed1103c61d4f3fbfac28ab8cdea9e2
Source dataset
uspto-grants-2013_05
Patent number
US08436000B2

Reaction notes

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