Hydrochloric Acid → N-{4-[(3R,4R,5S)-3-Amino-4-hydroxy-5-methylpiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxamide

HRID 1499594Notes

Reaction equation

HRID 1499594 reaction equation
[Si]([O:8][C@@H:9]1[C@@H:14]([CH3:15])[CH2:13][N:12]([C:16]2[C:21]([NH:22][C:23]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([C:32]4[C:37]([F:38])=[CH:36][C:35]([C:39]([OH:42])([CH3:41])[CH3:40])=[CH:34][C:33]=4[F:43])[N:26]=3)=[O:24])=[CH:20][N:19]=[C:18]3[O:44][CH2:45][CH2:46][C:17]=23)[CH2:11][C@H:10]1[NH:47]C(=O)OC(C)(C)C)(C(C)(C)C)(C)C.Cl.O1CCOCC1>>[NH2:47][C@H:10]1[C@H:9]([OH:8])[C@@H:14]([CH3:15])[CH2:13][N:12]([C:16]2[C:21]([NH:22][C:23]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([C:32]4[C:33]([F:43])=[CH:34][C:35]([C:39]([OH:42])([CH3:40])[CH3:41])=[CH:36][C:37]=4[F:38])[N:26]=3)=[O:24])=[CH:20][N:19]=[C:18]3[O:44][CH2:45][CH2:46][C:17]=23)[CH2:11]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86726808tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-{5-[({6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-2,3-dihydrofuro[2,3-b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate

Product 1

HCID 86726809N-{4-[(3R,4R,5S)-3-Amino-4-hydroxy-5-methylpiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxamide

Procedure

The amide intermediate prepared as described above was treated with 4.0 M HCl in dioxane (8 mL, 30 mmol) at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by preparative LCMS (Waters SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.) to give the title compound as a white powder. LCMS calc. for C28H31F3N5O4 (M+H)+ m/z=558.2. found: 558.0. 1H NMR (300 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.69 (s, 1H), 8.32 (m, 1H), 8.16 (m, 1H), 7.32 (d, J=9.0 Hz, 2H), 5.27 (br s, 1H), 4.49 (m, 3H), 3.05 (m, 1H), 2.96 (m, 1H), 2.66-2.42 (m, 5H), 1.47 (s, 6H), 0.68 (d, J=6.6 Hz, 3H) ppm.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe resulting residue was purified by preparative LCMS (Waters SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size
  3. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-bb274abc972c4e48935e62a361a0e7a3
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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