Water → HCID 71526726, compound

HRID 540477Notes

Reaction equation

HRID 540477 reaction equation
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([C@@H:13]2[C@@H:17]3[CH2:18][CH2:19][CH2:20][C@@H:21]([C:22]4[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=4[C:32]4[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[C:34]([CH2:40][CH2:41][C:42]([NH:44][NH2:45])=[O:43])[CH:33]=4)[N:16]3[C:15](=[O:46])[O:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(=O)(O)[O-].[Na+].O.[N:55]#[C:56]Br>O1CCOCC1>[NH2:55][C:56]1[O:43][C:42]([CH2:41][CH2:40][C:34]2[CH:35]=[CH:36][C:37]([O:38][CH3:39])=[C:32]([C:23]3[CH:24]=[CH:25][C:26]([C:28]([F:31])([F:30])[F:29])=[CH:27][C:22]=3[C@H:21]3[N:16]4[C:15](=[O:46])[O:14][C@H:13]([C:5]5[CH:4]=[C:3]([C:2]([F:1])([F:47])[F:48])[CH:8]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:6]=5)[C@@H:17]4[CH2:18][CH2:19][CH2:20]3)[CH:33]=2)=[N:44][N:45]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 86682298HCID 86682298, compound

Product 1

HCID 71526726HCID 71526726, compoundYield 65,333.301%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To 3-[2′-{(1R,5S,8aS)-1-[3,5-bis(trifluoromethyl)phenyl]-3-oxohexahydro[1,3]oxazolo[3,4-a]pyridin-5-yl}-6-methoxy-4′-(trifluoromethyl)biphenyl-3-yl]propanehydrazide (10 mg, 0.015 mmol) in dioxane (1 mL) was added sodium bicarbonate (2.4 mg, 0.029 mmol) followed by water (0.2 mL). The system was sealed and cyanogen bromide (5.8 mL, 0.029 mmol) was added at room temperature. The reaction was complete in 5 minutes and the solvent was removed before the crude material was purified by HPLC to yield (1R,5S,8aS)-5-{5′-[2-(5-amino-1,3,4-oxadiazol-2-yl)ethyl]-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl}-1-[3,5-bis(trifluoromethyl)phenyl]hexahydro[1,3]oxazolo[3,4-a]pyridin-3-one (7 mg, 9.80 mmol). 1H NMR indicated that this compound exists as a pair of rotamers at 1:1 ratio. 1H NMR (500 MHz, CDCl3) δ8.45 (br s, 1H), 8.3 (br s, 1H), 7.90 (d, J=9.2 Hz, 1H), 7.75 (m, 5H), 7.38 (t, J=8.5 Hz) 7.2 (m, 2H), 7.0 (m, 2H), 5.55 (d, J=8.9 Hz, 1H), 5.40 (d, J=8.9 Hz, 1H), 5.38 (m, 1H), 5.25 (m, 1H), 4.2 (m, 1H), 3.95 (m, 1H), 3.82 (s, 3H), 3.8 (s, 3H), 3.2-3.1 (br s, 4H), 2.2 (m, 1H), 2.12 (m, 1H), 1.80 (m, 4H). MS ESI calc'd. for C33H28F9N4O4 [M+H]+ 715.2. found 715.3. RTA (95% HS): 1319 nM

Workup

  1. customThe system was sealed
  2. customthe solvent was removed before the crude material
  3. customwas purified by HPLC

Sources & evidence

ORD record
ord-24197f90dd4a4ca28de1582be3e5905c
Source dataset
uspto-grants-2014_10
Patent number
US08871738B2

Reaction notes

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