2,6-Lutidine → (3R*,5S*)-3-Amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

HRID 1698307Notes

Reaction equation

HRID 1698307 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:18]3[CH2:23][C@@H:22]([C:24](=[O:44])[N:25]([CH:41]4[CH2:43][CH2:42]4)[CH2:26][C:27]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[N:29]([CH2:36][CH2:37][CH2:38][O:39][CH3:40])[CH:28]=4)[CH2:21][C@@H:20]([NH:45]C(OC(C)(C)C)=O)[CH2:19]3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C1(NCC2C3C(=CC=CC=3)N(CCCOC)C=2)CC1.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>C(Cl)Cl>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([N:18]3[CH2:23][C@@H:22]([C:24](=[O:44])[N:25]([CH:41]4[CH2:43][CH2:42]4)[CH2:26][C:27]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[N:29]([CH2:36][CH2:37][CH2:38][O:39][CH3:40])[CH:28]=4)[CH2:21][C@@H:20]([NH2:45])[CH2:19]3)=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 59817701cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-amineHCID 69071487(3R*,5S*)-3-tert-butoxycarbonylamino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 57870324(3R*,5S*)-3-Amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred, ice-cooled solution of (3R*,5S*)-3-tert-butoxycarbonylamino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (prepared from cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-amine analogously as described in Example 59A) (1.2 g, 1.7 mmol) in CH2Cl2 (8 ml), 2,6-lutidine (0.79 mL, 6.8 mmol) is added followed by dropwise addition of trimethylsilyl trifluoromethanesulfonate (0.92 mL, 5.1 mmol). The cooling bath is removed, and the mixture is stirred at RT for 2.5 h. The reaction mixture is diluted with CH2Cl2 and washed with saturated NH4Cl solution. The organic layer is dried over Na2SO4 and evaporated in vacuo to afford the title compound as a brownish solid, which is used without further purification for the next steps. MS: 607.5 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, flow 1.5 ml/min): 6.05 min.

Workup

  1. customThe cooling bath is removed
  2. additionThe reaction mixture is diluted with CH2Cl2
  3. washwashed with saturated NH4Cl solution
  4. dry with materialThe organic layer is dried over Na2SO4
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-3ec60b860ce34cb0adf121474b5af5a3
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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