Hydrochloric Acid → (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-amine

HRID 1692025Notes

Reaction equation

HRID 1692025 reaction equation
Br[C:2]1[CH:21]=[CH:20][C:5]2[N:6]=[C:7]([N:9]3[CH2:13][CH2:12][C@@H:11]([N:14]4[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]4)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C[Si]([N-:39][Si](C)(C)C)(C)C.[Li+].Cl.[OH-].[Na+]>C1(C)C=CC=CC=1.CCOCC>[N:14]1([C@@H:11]2[CH2:12][CH2:13][N:9]([C:7]3[S:8][C:4]4[CH:3]=[C:2]([NH2:39])[CH:21]=[CH:20][C:5]=4[N:6]=3)[CH2:10]2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733832Lithium HexamethyldisilazideHCID 44124247(R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole

Product 1

HCID 66905493(R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-amine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of (R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole (Example 14, 100 mg, 0.273 mmol), tri-tert-butylphosphine (66.3 mg, 0.033 mmol), tris(dibenxylideneacetone)dipalladium(0) (12.5 mg, 0.014 mmol) and lithium bis(trimethylsilyl)amide (63.9 mg, 0.382 mmol) in toluene (1 ml) was heated in a microwave reactor to 160° C. for 30 minutes. The mixture was treated with HCl (1 N, 1 mL) and stirred for 5 minutes. It was then basified with NaOH (10%), diluted with ether and partitioned. The organic was separated, dried with MgSO4 and concentrated under reduced pressure. The residue was chromatographed on silica gel column eluting with 2% (9:1 methanol:concentrated NH4OH) in dichloromethane to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.43-1.52 (m, 2H), 1.58-1.68 (m, 4H), 1.91-2.07 (m, 1H), 2.20-2.34 (m, 1H), 2.39-2.56 (m, 4H), 2.90-3.05 (m, 1H), 3.39 (t, J=9.12 Hz, 1H), 3.46-3.58 (m, 3H), 3.66-3.76 (m, 1H), 3.82 (dd, J=9.52, 7.54 Hz, 1H), 6.69 (dd, J=8.33, 2.38 Hz, 1H), 6.96 (d, J=1.98 Hz, 1H), 7.39 (d, J=8.33 Hz, 1H); MS (DCI/NH3) m/z 303 (M+H)+.

Workup

  1. custompartitioned
  2. customThe organic was separated
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was chromatographed on silica gel column
  6. washeluting with 2% (9:1 methanol:concentrated NH4OH) in dichloromethane

Sources & evidence

ORD record
ord-c6d934f26f0a42f399a57bd0b5a8a784
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

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