Isopropanol → HCID 56963276, compound

HRID 1184956Notes

Reaction equation

Cl.Cl.[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@@H:11]1[CH2:21][CH2:20][C@@H:19]([O:22][Si](C(C)C)(C(C)C)C(C)C)[C:14]2=[N:15][CH:16]=[CH:17][CH:18]=[C:13]2[CH:12]1[NH2:33].C(O)(C)C>O>[NH2:33][CH:12]1[C:13]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[C@H:19]([OH:22])[CH2:20][CH2:21][C@H:11]1[C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([F:10])[C:4]=1[F:3]

Participants

Conditions

Temperature: 82 °C

Procedure

To a 250 ml flask was charged (6S,9R)-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-amine di HCl salt (15 g, 25.88 mmol) and a solution of isopropanol:water (45 mL:15 mL). The mixture was heated to 82° C. for 6 h then dried via azeotropic distillation at atmospheric pressure using isopropanol until the KF was less than <3%. After fresh isopropanol (25 ml) was added, the mixture was heated to 70° C. and then isopropyl acetate (45 ml) was added that resulting in a white slurry. The slurry cooled to 22° C. for 15 min to afford a white solid (9.33 g, 99%). 1H NMR (500 MHz CD3OD) δ 8.77 (d, J=5.7 Hz, 1H), 8.47 (d, J=7.9 Hz, 1H), 8.11 (dd, J=6.0, 8.2 Hz, 1H), 7.21-7.32 (m, 3H), 5.53 (dd, J=3.8, 9.8 Hz, 1H) 5.33 (d, J=9.8 Hz, 1H), 3.5 (bm, 1H), 2.25-2.40 (m, 2H), 2.15 (bm, 1H), 1.90 (bm, 1H); 13C NMR (125 MHz, MeOD) δ 159.4, 153.9, 151.9 and 151.8, 149.7, 143.6, 141.8, 135.7, 130.6, 127.7, 126.8, 118.9, 70.0, 54.9, 42.2, 34.5, 33.4.

Workup

customthen dried via azeotropic distillation at atmospheric pressure
additionAfter fresh isopropanol (25 ml) was added
temperaturethe mixture was heated to 70° C.
additionisopropyl acetate (45 ml) was added
customthat resulting in a white slurry
temperatureThe slurry cooled to 22° C. for 15 min

Sources & evidence

ORD record: ord-e672fee7a403473795794b4044661e73
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669368B2

Reaction notes

Loading…