Methanol → Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

HRID 712162Notes

Reaction equation

HRID 712162 reaction equation
[Br:1][C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:7][C:6]=2[CH:5]=[C:4](I)[CH:3]=1.[CH3:18][C:19]1([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:24][CH2:23][N:22]([C:25]2[N:30]=[CH:29][C:28](B3OC(C)(C)C(C)(C)O3)=[CH:27][N:26]=2)[CH2:21][CH2:20]1.CO.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:7][C:6]=2[CH:5]=[C:4]([C:28]2[CH:27]=[N:26][C:25]([N:22]3[CH2:23][CH2:24][C:19]([CH3:18])([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:20][CH2:21]3)=[N:30][CH:29]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 62657Potassium Phosphate, TribasicHCID 578137231-(7-Bromo-5-iodobenzo[d]thiazol-2-yl)-3-ethylureaHCID 66976878Ethyl 4-methyl-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperidine-4-carboxylate

Product 1

HCID 86663956Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylateYield 41.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-(7-bromo-5-iodobenzo[d]thiazol-2-yl)-3-ethylurea (22.7 g, 53.20 mmol) and ethyl 4-methyl-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperidine-4-carboxylate (20 g, 53.2 mmol) in 1,4-dioxane:MeOH (300:180 mL) was added potassium phosphate (17 g, 79 mmol) at rt. The resulting mixture was degassed for 15-20 min by purging N2 followed by addition of tetrakis(triphenylphosphine)palladium(0) (6.1 g, 5.32 mmol). The reaction mixture was again degassed for another 15-20 min then heated up to 80° C. or 5 h. After completion of reaction (by TLC), the reaction was cooled to rt, diluted with EtOAc (500 mL) and passed through celite. The filtrate was evaporated and the crude residue purified over 100-200 M silica-gel by using 1.50% MeOH: DCM to obtain the desired product as an off-white solid (12 g, 41%). 1H NMR (DMSO-d6): δ 1.09 (t, J=7.20 Hz, 3H), 1.20 (m, 6H), 1.45 (m, 2H), 2.03 (m, 2H), 3.16 (m, 2H), 3.30 (q, J=7.20, 2H), 4.12 (q, J=6.80 Hz, 2H), 4.25 (m, 2H), 6.75 (br s, 1H), 7.69 (s, 1H), 7.86 (s, 1H); 8.75 (s, 2H) and 10.91 (br s, 1H). MS: 547.11 [M+H]+.

Workup

  1. customThe resulting mixture was degassed for 15-20 min
  2. customby purging N2
  3. customThe reaction mixture was again degassed for another 15-20 min
  4. customAfter completion of reaction (by TLC)
  5. temperaturethe reaction was cooled to rt
  6. customThe filtrate was evaporated
  7. customthe crude residue purified over 100-200 M silica-gel

Sources & evidence

ORD record
ord-aba119021fe047c197d55f78a9e86228
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

Loading…