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Azetidine → 5-(Azetidin-1-ylsulfonyl)-2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole

HRID 1435413
Notes
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Reaction equation

HRID 1435413 reaction equation
[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:8]2[CH:17]=[CH:18][C:19]([S:21](Cl)(=[O:23])=[O:22])=[CH:20][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:25]1[CH2:28][CH2:27][CH2:26]1>CN(C1C=CN=CC=1)C.CC#N>[N:25]1([S:21]([C:19]2[CH:18]=[CH:17][C:8]3[N:9]([CH2:10][CH:11]4[CH2:16][CH2:15][O:14][CH2:13][CH2:12]4)[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[N:6][C:7]=3[CH:20]=2)(=[O:23])=[O:22])[CH2:28][CH2:27][CH2:26]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 10422AzetidineHCID 579372982-tert-Butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride

Product 1

HCID 236593015-(Azetidin-1-ylsulfonyl)-2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342Acetonitrile
Solvent

Procedure

Following the same procedure in Example 1, Step A, using 2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride (76 mg, 0.20 mmol), azetidine (34 uL, 26 mg, 0.50 mmol) and DMAP (82 mg, 0.67 mmol) in MeCN (5 mL). The crude product was purified by MPLC using Hex/EtOAc (1:2) on silica gel to give 37 mg (46% yield) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 1.52-1.65 (m, 4 H), 1.68 (s, 9 H), 1.99-2.13 (m, 2 H), 2.32-2.47 (m, 1 H), 3.32-3.43 (m, 2 H), 3.74-3.84 (m, 4 H), 3.90-4.01 (m, 2 H), 4.54 (d, J=7.42 Hz, 2 H), 7.92 (dd, J=8.79, 1.56 Hz, 1 H), 8.09 (d, J=8.79 Hz, 1 H), 8.15 (d, J=1.17 Hz, 1 H); MS (ESI) (M+H)+=392.0; Anal. Calcd for C20H29N3O3S+1.20 TFA+0.40 EtOAc+0.1H2O (556.60): C, 50.93; H, 5.94; N, 7.55. Found: C, 50.98; H, 5.68; N, 7.50.

Workup

  1. customThe crude product was purified by MPLC

Sources & evidence

ORD record
ord-7ee95019ea854ca28dfcdeb38cb719e6
Source dataset
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07615642B2

Reaction notes

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