Methanol → 5-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(pyridin-2-yloxy)-phenyl]-amino}-thiophene-2-carboxylic acid

HRID 1046413Notes

Reaction equation

C[O:2][C:3]([C:5]1[S:6][C:7]([C:33]#[C:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:8][C:9]=1[N:10]([C:24]([CH:26]1[CH2:31][CH2:30][CH:29]([CH3:32])[CH2:28][CH2:27]1)=[O:25])[C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:13][CH:12]=1)=[O:4].C1COCC1.CO.O.[OH-].[Li+]>O>[CH3:36][C:35]([CH3:37])([CH3:38])[C:34]#[C:33][C:7]1[S:6][C:5]([C:3]([OH:4])=[O:2])=[C:9]([N:10]([C:24]([CH:26]2[CH2:27][CH2:28][CH:29]([CH3:32])[CH2:30][CH2:31]2)=[O:25])[C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[CH:15][CH:16]=2)[CH:8]=1

Participants

Conditions

Temperature: 60 °C

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(pyridin-2-yloxy)-phenyl]-amino}-thiophene-2-carboxylic acid methyl ester (174 mg, 0.33 mmol) in a 3:2:1 mixture of THF:MeOH:water (5 mL) was treated with lithium hydroxide monohydrate (0.69 g, 1.65 mmol) and heated to 60° C. for 1 hour. The organic volatiles were evaporated under reduced pressure and the crude material was purified by reverse-phase HPLC to afford the title compound in 70% yield. MS (m/z): 517.0 [M+H]−; HPLC retention time: 4.90 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

Workup

customThe organic volatiles were evaporated under reduced pressure
customthe crude material was purified by reverse-phase HPLC

Sources & evidence

ORD record: ord-a60b1e27fe0f414994bea4f3a36ec62a
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569302B2

Reaction notes

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