Nitrogen → 1-[5-[2-(ethylcarbamoylamino)-7-[(E)-methoxyiminomethyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methylpiperidine-4-carboxylic acid

HRID 712272Notes

Reaction equation

HRID 712272 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9](/[CH:22]=[N:23]/[O:24][CH3:25])[C:10]2[S:14][C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:12][C:11]=2[CH:21]=1)(=O)=O.C([O-])(=O)C.[K+].N#N.Br[C:36]1[CH:37]=[N:38][C:39]([N:42]2[CH2:47][CH2:46][C:45]([CH3:51])([C:48]([OH:50])=[O:49])[CH2:44][CH2:43]2)=[N:40][CH:41]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:19]([NH:18][C:16](=[O:17])[NH:15][C:13]1[S:14][C:10]2[C:9](/[CH:22]=[N:23]/[O:24][CH3:25])=[CH:8][C:7]([C:36]3[CH:41]=[N:40][C:39]([N:42]4[CH2:47][CH2:46][C:45]([CH3:51])([C:48]([OH:50])=[O:49])[CH2:44][CH2:43]4)=[N:38][CH:37]=3)=[CH:21][C:11]=2[N:12]=1)[CH3:20]

Participants

8

Reactant 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 669772191-(5-Bromopyrimidin-2-yl)-4-methylpiperidine-4-carboxylic acidHCID 87222484[2-(ethylcarbamoylamino)-7-[(E)-methoxyiminomethyl]-1,3-benzothiazol-5-yl] trifluoromethanesulfonate

Product 1

HCID 569527251-[5-[2-(ethylcarbamoylamino)-7-[(E)-methoxyiminomethyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methylpiperidine-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A stirred solution of (E)-2-(3-ethylureido)-7-((methoxyimino)methyl)benzo[d]thiazol-5-yl trifluoromethanesulfonate (225 mg, 0.34 mmol), bis(neopentyl)glycolatodiboron (180 mg, 0.8 mmol) and potassium acetate (100 mg, 1.02 mmol) in anhydrous DMF (3.5 ml) was purged with N2 for 15 min. 1,1′-bis(diphenylphosphino)ferrocene palladium(II)chloride (30 mg, 0.034 mmol) was added, the reaction vessel was sealed and heated at 80° C. for 2 h. The reaction mixture was cooled to ambient temperature, treated with 1-(5-bromopyrimidin-2-yl)-4-methylpiperidine-4-carboxylic acid (120 mg, 0.4 mmol) followed by aqueous cesium carbonate solution (3.7M 0.5 ml, 0.343 mmol). The reaction mixture was purged with N2 for 5 min, treated with 1,1′-bis(diphenylphosphino)ferrocene palladium(II)chloride (30 mg, 0.034 mmol), sealed and heated at 80° C. for 2 h. The reaction was allowed to cool, filtered and Compound 72 purified by preperative HPLC as a brown solid (40 mg, LC-MS indicated 97% purity) (24%). 1H NMR (CH3OH-d4): δ 8.67 (2H, s), 8.40 (1H, s), 7.86 (1H, d, J=1.66 Hz), 7.53 (1H, d, J=1.67 Hz), 4.42 (2H, dt, J=13.74, 4.26 Hz), 4.11 (3H, s), 3.45-3.32 (2H, m), 2.21 (2H, dt, J=13.45, 3.31 Hz), 1.49 (2H, ddd, J=13.45, 10.71, 4.04 Hz), 1.30 (3H, s), 1.26 (3H, t, J=7.28 Hz). MS: 498 [M+H]+

Workup

  1. customthe reaction vessel was sealed
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. customThe reaction mixture was purged with N2 for 5 min
  4. customsealed
  5. temperatureheated at 80° C. for 2 h
  6. temperatureto cool
  7. filtrationfiltered
  8. customCompound 72 purified by preperative HPLC as a brown solid (40 mg, LC-MS indicated 97% purity) (24%)

Sources & evidence

ORD record
ord-bafc6066a6a646eaa825a624e9e52f82
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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