Acetic Acid → 6-(1-methyl-1H-pyrazol-4-yl)-2-(3-(pyrrolidin-1-yl)azetidin-1-yl)benzo[d]thiazole

HRID 2040965Notes

Reaction equation

HRID 2040965 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:20]=[CH:19][C:10]3[N:11]=[C:12]([N:14]4[CH2:17][C:16](=O)[CH2:15]4)[S:13][C:9]=3[CH:8]=2)[CH:4]=[N:3]1.[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1(C)C=CC=CC=1>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:20]=[CH:19][C:10]3[N:11]=[C:12]([N:14]4[CH2:17][CH:16]([N:21]5[CH2:25][CH2:24][CH2:23][CH2:22]5)[CH2:15]4)[S:13][C:9]=3[CH:8]=2)[CH:4]=[N:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 669058091-(6-(1-methyl-1H-pyrazol-4-yl)benzo[d]thiazol-2-yl)azetidin-3-one

Product 1

HCID 441241276-(1-methyl-1H-pyrazol-4-yl)-2-(3-(pyrrolidin-1-yl)azetidin-1-yl)benzo[d]thiazole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 1-(6-(1-methyl-1H-pyrazol-4-yl)benzo[d]thiazol-2-yl)azetidin-3-one (Reference Example 4, 17 mg, 0.06 mmol), pyrrolidine (0.015 mL, 0.18 mmol), and a catalytic amount of acetic acid (0.005 mL) in toluene (0.4 mL) was stirred at room temperature for 5 minutes, then sodium triacetoxyborohydride (38 mg, 0.18 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was then quenched with 1 M aqueous K3PO4 (0.4 mL), and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated. The crude product was purified by silica gel chromatography (60:40 dichloromethane/acetonitrile to 56:40:4 dichloromethane/acetonitrile/methanol) to give 6-(1-methyl-1H-pyrazol-4-yl)-2-(3-(pyrrolidin-1-yl)azetidin-1-yl)benzo[d]thiazole. 1H NMR (300 MHz, CD3OD) δ ppm 1.84-1.90 (m, 4H), 2.59-2.66 (m, 4H), 3.59-3.68 (m, 1H), 3.92 (s, 3H), 4.06-4.12 (m, 2H), 4.26-4.32 (m, 2H), 7.45 (dd, J=1, 8 Hz, 1H), 7.50 (dd, J=2, 8 Hz, 1H), 7.79 (d, J=1 Hz, 1H), 7.85 (d, J=2 Hz, 1H), 7.92 (d, J=1 Hz, 1H); MS (ESI) m/z 340 (M+H)+.

Workup

  1. customThe reaction mixture was then quenched with 1 M aqueous K3PO4 (0.4 mL)
  2. extractionextracted twice with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (60:40 dichloromethane/acetonitrile to 56:40:4 dichloromethane/acetonitrile/methanol)

Sources & evidence

ORD record
ord-705c9dd5515f4ba78bbcd50f2fc81eb7
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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