Potassium Carbonate → 4-[5-(6-Amino-5-benzothiazol-2-ylpyridin-3-yl)-thiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1926340Notes

Reaction equation

HRID 1926340 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[S:15][C:16](Br)=[CH:17][N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=[C:21]1[C:29]1[C:30]([NH2:44])=[N:31][CH:32]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:34]=1.C(=O)([O-])[O-].[K+].[K+]>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.COCCOC.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[S:15][C:16]([C:33]3[CH:32]=[N:31][C:30]([NH2:44])=[C:29]([C:21]4[S:20][C:24]5[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=5[N:22]=4)[CH:34]=3)=[CH:17][N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 34180719Tert-butyl 4-(5-bromo-1,3-thiazol-2-yl)piperazine-1-carboxylateHCID 574165133-(1,3-Benzothiazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

Product 1

HCID 675212144-[5-(6-Amino-5-benzothiazol-2-ylpyridin-3-yl)-thiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-(5-bromothiazol-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (0.079 g, 0.229 mmol), 3-benzothiazol-2-yl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyridin-2-ylamine (BB8) (0.105 g, 0.298 mmol), potassium carbonate (0.101 g, 0.732 mmol), and Pd(PPh3)4 (0.018 g, 0.016 mmol) in previously degassed DME/H2O (4:1) (4.0 mL) was placed in a microwave tube and evacuated and charged with N2 (2×). The reaction mixture was heated in the microwave reactor to 100° C. for 30 min. The reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified on prep-TLC eluting with 3% 7M NH3 in MeOH/DCM yielding 4-[5-(6-amino-5-benzothiazol-2-ylpyridin-3-yl)-thiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl ester, MS (ES+): m/z=495.06 [MH+]. To a solution of this compound in DCM (1.0 mL) was added 1M HCl in ether (2.0 mL, 2.0 mmol), and the mixture was stirred at room temperature overnight. The solid that formed was filtered off and purified on the MDP. To a solution of the material thus obtained in DCM (1.0 mL) was added 1M HCl in ether (1.0 mL, 1.0 mmol). The precipitate was filtered off and dried in vacuo, yielding the title compound as yellow solid. 1H NMR (400 MHz, CD3OD): δ=2.95-3.00 (m, 4H), 3.46-3.53 (m, 4H), 7.40 (s, 1H), 7.42-7.48 (m, 1H), 7.53 (dd, J=15.3, 1.1 Hz, 1H), 7.98-8.05 (m, 2H), 8.07 (d, J=2.3 Hz, 1H), 8.23 (d, J=2.3 Hz, 1H). MS (ES+): m/z=395.06 (55) [MH+]. HPLC: tR=2.11 min (ZQ2, polar—5 min).

Workup

  1. customevacuated
  2. additioncharged with N2 (2×)
  3. additionThe reaction mixture was diluted with EtOAc
  4. washwashed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified
  9. washon prep-TLC eluting with 3% 7M NH3 in MeOH/DCM

Sources & evidence

ORD record
ord-3c90b5b810694d5396a3e8fa90464f84
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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