Trifluoroacetic acid → HCID 178476806, compound

HRID 2279906Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][CH2:18][CH:19]([PH:21](=[O:25])[O:22][CH2:23][CH3:24])[CH3:20])=[CH:15][C:14]=2[O:28][CH3:29])[N:3]=1.[NH2:30][C:31]1[C:32]([C:38]([NH:40][CH3:41])=[O:39])=[N:33][C:34]([Br:37])=[CH:35][CH:36]=1.C(O)(C(F)(F)F)=O>>[Br:37][C:34]1[N:33]=[C:32]([C:38](=[O:39])[NH:40][CH3:41])[C:31]([NH:30][C:2]2[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]3[CH:27]=[CH:26][C:16]([CH2:17][CH2:18][CH:19]([PH:21](=[O:25])[O:22][CH2:23][CH3:24])[CH3:20])=[CH:15][C:14]=3[O:28][CH3:29])[N:3]=2)=[CH:36][CH:35]=1

Participants

Reactant 3

HCID 6422Trifluoroacetic acid

HCID 866976863-Amino-6-bromo-N-methylpicolinamide2×

HCID 178476804HCID 178476804, compound2×

Product 1

HCID 178476806HCID 178476806, compoundYield 61%

Conditions

Temperature: 80 °C

Procedure

A solution of ethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)propan-2-ylphosphinate (Compound 68D, 1.00 g, 2.21 mmol) and 3-amino-6-bromo-N-methylpyridine-2-carboxamide (Compound 6D, 0.516 g, 2.24 mmol) in TFE (11.71 mL) was charged with TFA (0.341 mL, 4.43 mmol). The reaction mixture was heated at 80° C. for 16 hours. The reaction mixture was concentrated under reduced pressure to a light yellow oil. The crude material was purified using a Teledyne ISCO Combiflash® Rf system using DCM/MeOH (100:0→95:5) as eluent to afford the desired product as a white solid (865 mg, 61%). 1H NMR (CDCl3, 400 MHz): δ 12.97 (br. s., 1H), 8.85 (d, J=9.3 Hz, 1H), 8.29 (s, 1H), 8.13 (q, J=4.4 Hz, 1H), 7.66 (br. s., 1H), 7.59 (d, J=9.1 Hz, 1H), 7.02 (t, J=1.6 Hz, 1H), 6.88 (td, J=1.8, 8.2 Hz, 1H), 3.92-4.10 (m, 2H), 3.87 (s, 3H), 3.19 (dd, J=2.8, 14.9 Hz, 2H), 3.04 (d, J=5.3 Hz, 3H), 1.87-2.00 (m, 1H), 1.18-1.27 (m, 9H). MS (ESI): m/z 645.55/647.54 [M+H]+. UPLC: tR=1.47 min (UPLC-SQD: analytical—2 min).

Workup

concentrationThe reaction mixture was concentrated under reduced pressure to a light yellow oil
customThe crude material was purified

Sources & evidence

ORD record: ord-3f7f3dde88f3436b9492e5feba7f33d4
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133224B2

Reaction notes

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