Trifluoroacetic acid → HCID 73213799, compound

HRID 1398347Notes

Reaction equation

HRID 1398347 reaction equation
COC1C=CC(C[NH:8][C:9]2[N:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[C:17](=[O:19])[N:16]([CH3:20])[C:15]2[CH:21]=[C:22]([O:25][CH2:26][C@@H:27]([NH:32]C(=O)OC(C)(C)C)[CH2:28][CH:29]([CH3:31])[CH3:30])[CH:23]=[CH:24][C:14]3=2)=CC=1.[C:42]([OH:48])([C:44]([F:47])([F:46])[F:45])=[O:43]>C(Cl)Cl.O.C(#N)C>[C:42]([OH:48])([C:44]([F:47])([F:46])[F:45])=[O:43].[NH2:8][C:9]1[N:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[C:17](=[O:19])[N:16]([CH3:20])[C:15]1[CH:21]=[C:22]([O:25][CH2:26][C@@H:27]([NH2:32])[CH2:28][CH:29]([CH3:30])[CH3:31])[CH:23]=[CH:24][C:14]2=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 86710345HCID 86710345, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 73213799HCID 73213799, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
45 °C

Procedure

To a stirred solution of (S)-tert-butyl (1-((4-((4-methoxybenzyl)amino)-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (100 mg, 0.145 mmol) in DCM (10 mL) at rt was added TFA (4 mL, 51.9 mmol) dropwise and the reaction was heated at 45° C. for 12 h. After the completion of reaction, the volatile organics were evaporated under reduced pressure and the residue obtained was purified by prep. HPLC (0.1% TFA in water/acetonitrile as mobile phase) to yield (S)-4-amino-8-((2-amino-4-methylpentyl)oxy)-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (16 mg, 0.046 mmol, 32% yield) as a mono TFA salt as an off white solid. LC/MS (ESI) m/e 341.2 [(M+H)+, calcd for C19H25N4O2 341.2]; LC/MS retention time (method B): tR=1.08 min; HPLC retention time (method A): tR=8.02 min; HPLC retention time (method B): tR=8.40 min; 1H NMR (400 MHz, MeOD) δ 8.44 (d, J=8.80 Hz, 1H), 8.00 (d, J=7.20 Hz, 1H), 7.71 (d, J=7.20 Hz, 1H), 7.24 (d, J=2.40 Hz, 1H), 7.21-7.22 (m, 1H), 4.51 (dd, J=3.20, 10.80 Hz, 1H), 4.34 (dd, J=6.40, 10.40 Hz, 1H), 3.84 (s, 3H), 3.78-3.82 (m, 1H), 1.65-1.89 (m, 3H), 1.08 (d, J=4.40 Hz, 3H), 1.06 (d, J=4.40 Hz, 3H).

Workup

  1. customAfter the completion of reaction
  2. customthe volatile organics were evaporated under reduced pressure
  3. customthe residue obtained
  4. customwas purified by prep

Sources & evidence

ORD record
ord-37c5edfbec964e65b00d7b2f1ac464f5
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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