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

HRID 1926363Notes

Reaction equation

HRID 1926363 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:25])=[N:12][CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1.[C:26]([O:30][C:31]([N:33]1[CH2:36][CH:35]([N:37]2[CH:41]=[C:40](I)[CH:39]=[N:38]2)[CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:26]([O:30][C:31]([N:33]1[CH2:36][CH:35]([N:37]2[CH:41]=[C:40]([C:14]3[CH:13]=[N:12][C:11]([NH2:25])=[C:10]([C:2]4[S:1][C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=5[N:3]=4)[CH:15]=3)[CH:39]=[N:38]2)[CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 574165133-(1,3-Benzothiazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 58431448tert-butyl 3-(4-iodo-1H-pyrazol-1-yl)azetidine-1-carboxylate

Product 1

HCID 675207313-[4-(6-Amino-5-benzothiazol-2-ylpyridin-3-yl)-pyrazol-1-yl]-azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-benzothiazol-2-yl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-ylamine (BB8) (30 mg, 0.080 mmol), 3-(4-iodopyrazol-1-yl)-azetidine-1-carboxylic acid tert-butyl ester (59 mg, 0.17 mmol), potassium carbonate (40 mg, 0.20 mmol), and Pd(dppf)Cl2 (3 mg, 0.01 mmol) in 1,4-dioxane (1.5 mL) and H2O (0.5 mL) was left to stir at 100° C. for 30 min in the microwave reactor. The mixture was passed through PL-Thiol MP SPE and the residue was concentrated in vacuo. The resulting oil was partitioned between EtOAc and water (3×). The combined organic extracts were treated with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by prep TLC (EtOAc:hexane (3:2)), giving 3-[4-(6-Amino-5-benzothiazol-2-ylpyridin-3-yl)-pyrazol-1-yl]-azetidine-1-carboxylic acid tert-butyl ester, MS (ES+): m/z=449 [MH+]. This material was left to stir at rt in a (1:1) DCM:TFA mixture for 15 min. The solid that formed was filtered off and dried in vacuo, affording the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ=4.53 (d, J=8.1 Hz, 1H), 4.58 (d, J=7.3 Hz, 4H), 5.49 (quint, J=7.4 Hz, 1H), 7.49-7.56 (m, 1H), 7.60 (dd, J=15.4, 1.3 Hz, 1H), 8.07 (d, J=8.1 Hz, 1H), 8.12 (d, J=7.8 Hz, 1H), 8.16 (s, 1H), 8.21 (s, 1H), 8.33 (d, J=2.3 Hz, 1H), 8.57 (d, J=2.0 Hz, 1H). MS (ES+): m/z=349.16 (100) [MH+]. HPLC: tR=1.99 min (ZQ2, polar—5 min).

Workup

  1. concentrationthe residue was concentrated in vacuo
  2. customThe resulting oil was partitioned between EtOAc and water (3×)
  3. additionThe combined organic extracts were treated with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by prep TLC (EtOAc:hexane (3:2))

Sources & evidence

ORD record
ord-6bb25aff066244e490d9228763d57bf1
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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