Trifluoroacetic acid → HCID 57911461, compound

HRID 1666154Notes

Reaction equation

HRID 1666154 reaction equation
[O:1]=[C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[N:3]1[CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C@H:20]2[C:26]3=[N:27][C:28]([NH:31]C(C)(C)C)=[CH:29][CH:30]=[C:25]3[CH2:24][C@H:23]([C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[C:37]=3[F:43])[CH2:22][CH2:21]2)=[O:18])[CH2:13][CH2:12]1.C(O)(C(F)(F)F)=O>>[O:1]=[C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[N:3]1[CH:11]1[CH2:12][CH2:13][N:14]([C:17]([O:19][C@H:20]2[C:26]3=[N:27][C:28]([NH2:31])=[CH:29][CH:30]=[C:25]3[CH2:24][C@H:23]([C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[C:37]=3[F:43])[CH2:22][CH2:21]2)=[O:18])[CH2:15][CH2:16]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57911435HCID 57911435, compound

Product 1

HCID 57911461HCID 57911461, compound

Conditions

Temperature
70 °C

Procedure

The mixture of (6R,9R)-2-(tert-butylamino)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (0.1537 g, 0.117 mmol) and TFA (4 mL, 1.18E+04 mmol) was heat to 70° C. for 1 hour. LCMS showed that most of the starting material was converted to the desired product. There was no sign of hydrolysis of the carbamate to alcohol. TFA was removed via vacuum and the crude was partitioned between ethyl acetate and NaOH (1N). The ethyl acetate layer was separated, dried (Na2SO4), filtered and concentrated. Flash column by methanol in CH2Cl2 from 0 to 3.5% to 5%. At this point the desired product was not eluted out. The flash column was continued to eluted with 5% methanol in CH2Cl2 to gave the desired product as a white solid (64.8 mg, 90%). MS(ESI)[M+H+]=535; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 11.44 (br.s., 1H) 8.13 (d, J=4.53 Hz, 1H) 7.36 (br.s., 1H) 7.14-7.24 (m, 1H) 6.99-7.10 (m, 4H) 6.37 (d, J=7.55 Hz, 1H) 5.87 (d, J=10.32 Hz, 1H) 5.57 (d, J=1.51 Hz, 1H) 4.48-4.83 (m, 2H) 4.17 (br.s., 1H) 3.23 (dd, J=13.72, 11.96 Hz, 1H) 2.95 (d, J=10.32 Hz, 3H) 2.69 (d, J=14.10 Hz, 2H) 2.08-2.31 (m, 3H) 1.83-2.08 (m, 3H) 1.19-1.35 (m, 1H) 0.81-0.95 (m, 1H).

Sources & evidence

ORD record
ord-2d473853ce034dd5b63a350a7438c202
Source dataset
uspto-grants-2011_10
Patent number
US08044043B2

Reaction notes

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