2-Chloroacetamidine → HCID 178520004, compound

HRID 1485363Notes

Reaction equation

C[O-:2].[Na+].C(O[C:7]([CH:9]1[C:15](=O)[CH2:14][CH2:13][N:12]([C:17]2[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:11][CH2:10]1)=[O:8])C.Cl[CH2:28][C:29]([NH2:31])=[NH:30]>CO>[OH:2][CH2:28][C:29]1[N:31]=[C:7]([OH:8])[C:9]2[CH2:10][CH2:11][N:12]([C:17]3[C:22]([C:23]([F:24])([F:25])[F:26])=[CH:21][CH:20]=[CH:19][N:18]=3)[CH2:13][CH2:14][C:15]=2[N:30]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To solution of NaOMe (1.9 mL) in MeOH (0.5 mL) was added 5-oxo-1-(3-trifluoromethyl-pyridin-2-yl)-azepane-4-carboxylic acid ethyl ester (Intermediate B; 285 mg, 0.96 mmol), followed by 2-chloro-acetamidine (149 mg, 1.16 mmol). After heating at 100° C. in a microwave for 15 min, the mixture was cooled and concentrated. The residue was dissolved in water and extracted with CH2Cl2. The combined organic layers were dried, concentrated, and directly purified using Preparative HPLC (conditions as in Example 54) to give the title compound (86 mg, 26%). MS (ESI): mass calcd. for C22H20F6N6O, 498.16; m/z found, 499.3 [M+H]+. 1H NMR (MeOD): 8.95 (d, J=2.3 Hz, 1H), 8.47-8.45 (m, 1H), 8.29 (dd, J=8.5, 2.2 Hz, 1H), 8.04 (dd, J=7.8, 1.7 Hz, 1H), 7.88 (d, J=8.6 Hz, 1H), 7.16 (dd, J=7.7, 4.9 Hz, 1H), 4.61 (s, 2H), 3.68-3.61 (m, 4H), 3.53 (s, 3H), 3.49-3.45 (m, 2H), 3.30-3.28 (m, 2H).

Workup

temperaturethe mixture was cooled
concentrationconcentrated
dissolutionThe residue was dissolved in water
extractionextracted with CH2Cl2
customThe combined organic layers were dried
concentrationconcentrated
customdirectly purified

Sources & evidence

ORD record: ord-44e6b96fc5a64ac4b7744d7a24c6675d
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422293B2

Reaction notes

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