Potassium tert-butoxide → 1-[5-[2-(Ethylcarbamoylamino)-7-[2-(3-methylimidazol-4-yl)ethynyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

HRID 712301Notes

Reaction equation

HRID 712301 reaction equation
CC(C)([O-])C.[K+].[CH2:7]([NH:9][C:10]([NH:12][C:13]1[S:14][C:15]2[C:21]([C:22]#[C:23][C:24]3[N:25]([CH3:29])[CH:26]=[N:27][CH:28]=3)=[CH:20][C:19]([C:30]3[CH:31]=[N:32][C:33]([N:36]4[CH2:41][CH2:40][C:39]([CH3:47])([C:42]([O:44]CC)=[O:43])[CH2:38][CH2:37]4)=[N:34][CH:35]=3)=[CH:18][C:16]=2[N:17]=1)=[O:11])[CH3:8]>CS(C)=O>[CH2:7]([NH:9][C:10]([NH:12][C:13]1[S:14][C:15]2[C:21]([C:22]#[C:23][C:24]3[N:25]([CH3:29])[CH:26]=[N:27][CH:28]=3)=[CH:20][C:19]([C:30]3[CH:35]=[N:34][C:33]([N:36]4[CH2:37][CH2:38][C:39]([CH3:47])([C:42]([OH:44])=[O:43])[CH2:40][CH2:41]4)=[N:32][CH:31]=3)=[CH:18][C:16]=2[N:17]=1)=[O:11])[CH3:8]

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 86664015Ethyl 1-[5-[2-(ethylcarbamoylamino)-7-[2-(3-methylimidazol-4-yl)ethynyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

Product 1

HCID 569534011-[5-[2-(Ethylcarbamoylamino)-7-[2-(3-methylimidazol-4-yl)ethynyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acidYield 29%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Potassium tertiary butoxide (150 mg, 1.35 mmol) was added to a solution of ethyl 1-[5-[2-(ethylcarbamoylamino)-7-[2-(3-methylimidazol-4-yl)ethynyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate in DMSO (1.5 mL). The mixture was stirred at rt for 2 h after which time LCMS indicated clean conversion to the acid. The mixture was filtered through cotton wool to remove solid particulates and purified by preparative-HPLC to give Compound 144 as a white solid, 43 mg, 29% yield for 2 steps. 1H NMR δ (ppm) (DMSO-d6): 8.81 (2H, s), 7.95 (1H, d, J=1.55 Hz), 7.89 (1H, s), 7.73 (1H, d, J=1.56 Hz), 7.45 (1H, s), 7.27 (1H, t, J=5.58 Hz), 4.32 (2H, dt, J=13.70, 4.46 Hz), 3.83 (3H, s), 3.37 (2H, ddd, J=14.10, 10.43, 4.06 Hz), 3.23 (2H, p, J=6.90 Hz), 2.06 (2H, dt, J=13.39, 3.62 Hz), 1.41 (2H, ddd, J=13.36, 10.05, 3.86 Hz), 1.21 (3H, s), 1.13 (3H, t, J=7.15 Hz). MS: 545 [M+H]+.

Workup

  1. filtrationThe mixture was filtered through cotton wool
  2. customto remove solid particulates
  3. custompurified by preparative-HPLC

Sources & evidence

ORD record
ord-9159d4edb7564573a008e2f7386ee237
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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