Sodium Hydroxide → 4-{[4-(2-Methyl-thiazol-4-ylmethoxy)-1H-indole-2-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 2267910Notes

Reaction equation

[CH3:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][O:8][C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[C:12]([C:18]([OH:20])=O)[NH:13]3)[N:6]=1.CC[N:23](C(C)C)C(C)C.[C:30]([O:34][C:35](=[O:43])NC1CCNCC1)([CH3:33])([CH3:32])[CH3:31].C1CN([P+](ON2N=[N:68][C:63]3[CH:64]=[CH:65][CH:66]=[CH:67]C2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[OH-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[C:30]([O:34][C:35]([N:68]1[CH2:63][CH2:64][CH:65]([NH:23][C:18]([C:12]2[NH:13][C:14]3[C:10]([CH:11]=2)=[C:9]([O:8][CH2:7][C:5]2[N:6]=[C:2]([CH3:1])[S:3][CH:4]=2)[CH:17]=[CH:16][CH:15]=3)=[O:20])[CH2:66][CH2:67]1)=[O:43])([CH3:33])([CH3:32])[CH3:31]

Participants

Conditions

Temperature: 0 °C

Procedure

4-(2-Methyl-thiazol-4-ylmethoxy)-1H-indole-2-carboxylic acid (170) (1.21 g, 4.2 mmol) is dissolved in 10 ml of DMF and the solution is cooled to 0° C. After addition of Huenigs base (2.16 ml, 12.6 mmol), piperidin-4-yl-carbamic acid tert-butyl ester (3) (841 mg, 4.2 mmol) and PyBOP (2.4 g, 4.6 mmol) the mixture is stirred at room temperature for 18 h. Ethyl acetate is added followed by concentrated sodium hydroxide, until a pH of 11 is reached. The organic layer is washed with brine, dried over sodium sulphate and evaporated under reduced pressure. The crude product is purified by flash-chromatography (silica gel, ethyl acetate/cyclohexane 1:1).

Workup

washThe organic layer is washed with brine
dry with materialdried over sodium sulphate
customevaporated under reduced pressure
customThe crude product is purified by flash-chromatography (silica gel, ethyl acetate/cyclohexane 1:1)

Sources & evidence

ORD record: ord-92b40e5319c64550bdb3ac8210136250
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858781B2

Reaction notes

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