1,2-Dichloroethane → HCID 49842490, compound

HRID 1968271Notes

Reaction equation

HRID 1968271 reaction equation
[F:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:16]([CH3:18])[CH3:17])[C:13]([OH:15])=O)[C:8](=[O:19])[C:7]3=[CH:20][NH:21][C:5]([C:6]=23)=[N:4][CH:3]=1.[C:22]([C:24]1([CH3:28])[CH2:27][NH:26][CH2:25]1)#[N:23].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C)C1C=CN=CC=1.CN(C=O)C>[F:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:16]([CH3:17])[CH3:18])[C:13]([N:26]3[CH2:27][C:24]([CH3:28])([C:22]#[N:23])[CH2:25]3)=[O:15])[C:8](=[O:19])[C:7]3=[CH:20][NH:21][C:5]([C:6]=23)=[N:4][CH:3]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 552994843-Methylazetidine-3-carbonitrileHCID 57389932(R)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid

Product 1

HCID 49842490HCID 49842490, compoundYield 47.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To an 8 mL scintillation vial equipped for stirring was added (R)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid (15 mg, 0.051 mmol). DMF (0.5 mL), 3-cyano-3-methylazetidine (15 mg, 0.077 mmol), HOBt (11.83 mg, 0.077 mmol), EDC (14.81 mg, 0.077 mmol) and N,N-dimethylpyridin-4-amine (9.44 mg, 0.077 mmol) were added and the solution was stirred at 25° C. for 4 h. The reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%). The fractions were collected and lyophilized to afford the title compound as a white solid (9 mg, 47.3%). 1H NMR (400 MHz, DMSO-d6) δ 0.79 (dd, J=6.69, 2.91 Hz, 3 H) 0.96 (dd, J=9.09, 6.57 Hz, 3 H) 1.41-1.73 (m, 3 H) 2.26-2.44 (m, 1 H) 3.85 (dd, J=15.66, 9.85 Hz, 1 H) 4.06 (d, J=9.35 Hz, 2 H) 4.61 (s, 1 H) 4.88 (dd, J=19.20, 6.82 Hz, 1 H) 5.03 (d, J=11.12 Hz, 1 H) 5.07-5.18 (m, 1 H) 7.99 (t, J=3.16 Hz, 1 H) 8.25 (t, J=2.65 Hz, 1 H) 12.40 (br. s., 1 H). [M+H] calc'd for C19H20FN5O2, 370; found, 370.5

Workup

  1. customTo an 8 mL scintillation vial equipped
  2. stirringthe solution was stirred at 25° C. for 4 h
  3. customThe reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%)
  4. customThe fractions were collected

Sources & evidence

ORD record
ord-c985fdd34b4c4596b3e010d05ceecea7
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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