Tetrahydrofuran → 7-(quinuclidin-4-ylmethyl)-8,9-dihydro-[1,4]diazepino[6,7,1-hi]indazol-6(7H)-one

HRID 2168560Notes

Reaction equation

HRID 2168560 reaction equation
N12CCC(C[NH:10][CH2:11][CH2:12][N:13]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][C:20]=4[C:22]([O-])=O)[CH:15]=[N:14]3)(CC1)CC2.[Li+].[CH:26]([N:29]([CH2:33][CH3:34])[CH:30]([CH3:32])C)([CH3:28])C.[CH3:35][CH2:36]CP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C1C[O:56]CC1>>[N:29]12[CH2:26][CH2:28][C:35]([CH2:36][CH:17]3[C:18](=[O:56])[CH:19]=[C:20]4[CH:22]=[N:10][CH:11]=[CH:12][N:13]5[C:21]4=[C:16]3[CH2:15][NH:14]5)([CH2:32][CH2:30]1)[CH2:34][CH2:33]2

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 66899618lithium 1-(2-(quinuclidin-4-ylmethylamino)ethyl)-1H-indazole-7-carboxylate

Product 1

HCID 708961797-(quinuclidin-4-ylmethyl)-8,9-dihydro-[1,4]diazepino[6,7,1-hi]indazol-6(7H)-oneYield 24%

Procedure

Lithium 1-(2-(quinuclidin-4-ylmethylamino)ethyl)-1H-indazole-7-carboxylate (1.2 g, 3.6 mmol) from Step G above in THF (30 mL) was cooled in an ice bath while N,N-diisopropylethylamine (4 mL, 21.6 mmol) was added, followed by 1-propanephosphonic acid cyclic anhydride (T3P; 50 wt % in EtOAc; 14 mL, 21.6 mmol). The reaction mixture was stirred at room temperature until the reaction was complete by TLC (overnight). The mixture was concentrated in vacuo and then purified with ISOLUTE® SCX-2 columns to give 7-(quinuclidin-4-ylmethyl)-8,9-dihydro-[1,4]diazepino[6,7,1-hi]indazol-6(7H)-one (267 mg, 24%).

Workup

  1. additionwas added
  2. customwas complete by TLC (overnight)
  3. concentrationThe mixture was concentrated in vacuo
  4. custompurified with ISOLUTE® SCX-2 columns

Sources & evidence

ORD record
ord-96312f8113f4440789e65c062fc11de2
Source dataset
uspto-grants-2015_06
Patent number
US09045501B2

Reaction notes

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