Dimethyl Sulfoxide → HCID 71227381, compound

HRID 715550Notes

Reaction equation

[F:1][C:2]([F:39])([F:38])S(O[C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([N:14]2[CH2:18][C@@:17]3([CH2:23][CH2:22][CH2:21][C@@:20]([CH2:25][N:26]4[C:30]5[CH:31]=[C:32]([C:35]#[N:36])[CH:33]=[CH:34][C:29]=5[N:28]=[CH:27]4)([CH3:24])[CH2:19]3)[O:16][C:15]2=[O:37])=[CH:9][N:8]=1)(=O)=O.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1.CS(C)=[O:48]>>[C:44]([OH:43])([C:2]([F:1])([F:38])[F:39])=[O:48].[CH3:24][C@:20]1([CH2:25][N:26]2[C:30]3[CH:31]=[C:32]([C:35]#[N:36])[CH:33]=[CH:34][C:29]=3[N:28]=[CH:27]2)[CH2:21][CH2:22][CH2:23][C@:17]2([O:16][C:15](=[O:37])[N:14]([C:10]3[CH:9]=[N:8][C:7]([N:40]4[CH2:45][CH2:44][O:43][CH2:42][CH2:41]4)=[CH:12][C:11]=3[CH3:13])[CH2:18]2)[CH2:19]1

Participants

Reactant 3

HCID 679Dimethyl Sulfoxide

HCID 8083Morpholine

HCID 86717598HCID 86717598, compound

Product 2

HCID 6422Trifluoroacetic acid

HCID 71227381HCID 71227381, compoundYield 46%

Conditions

Temperature: 100 °C

Procedure

A mixture of 5-((5S,7S)-7-((6-cyano-1H-benzo[d]imidazol-1-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-3-yl)-4-methylpyridin-2-yl trifluoromethanesulfonate (100 mg, 0.177 mmol) and morpholine (0.077 mL, 0.887 mmol) in Dimethyl Sulfoxide (DMSO) (1.5 mL) was heated in the microwave for 35 minutes at 100° C. The solution was purified by reverse phase HPLC (Waters Sunfire 30×150 mm Acetonitrile: Water 0.1% TFA 10-50%, 50 mL/min, 15 min) to afford the bis-TFA salt of 1-(((5S,7S)-7-methyl-3-(4-methyl-6-morpholinopyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (60 mg, 46%). 1H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 8.46 (s, 1H), 8.08 (s, 1H), 7.88 (d, J=8.28 Hz, 1H), 7.65 (dd, J=8.28, 1.25 Hz, 1H), 6.94 (s, 1H), 4.15-4.25 (m, 2H), 3.67-3.74 (m, 4H), 3.59 (s, 2H), 3.45-3.52 (m, 4H), 2.17 (s, 3H), 2.04 (d, J=13.55 Hz, 1H), 1.92 (d, J=14.56 Hz, 1H), 1.58-1.77 (m, 3H), 1.30-1.52 (m, 3H), 1.08 (s, 3H). MS (m/z) 501.3 (M+H+).

Workup

customThe solution was purified by reverse phase HPLC (Waters Sunfire 30×150 mm Acetonitrile: Water 0.1% TFA 10-50%, 50 mL/min, 15 min)

Sources & evidence

ORD record: ord-1fa6342d60e645578441aa33601b10ef
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187464B2

Reaction notes

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