Pivaloyl chloride → HCID 15984737, compound

HRID 1698328Notes

Reaction equation

HRID 1698328 reaction equation
C1C2C(COC([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)C3C(=CC=CC=3)C=2C=CC=1.C(N(C(C)C)C(C)C)C.[C:55](Cl)(=[O:60])[C:56]([CH3:59])([CH3:58])[CH3:57]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH:41]1([N:25]([CH2:26][C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]([CH2:36][CH2:37][CH2:38][O:39][CH3:40])[CH:28]=2)[C:24]([C@@H:22]2[CH2:21][C@H:20]([NH:45][C:55](=[O:60])[C:56]([CH3:59])([CH3:58])[CH3:57])[CH2:19][NH:18][CH2:23]2)=[O:44])[CH2:42][CH2:43]1

Participants

6

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 67274027(3S,5R)-3-amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 15984737HCID 15984737, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred mixture of (3S,5R)-3-amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (374 mg, 0.62 mmol), N-ethyldiisopropylamine (503 μl, 2.94 mmol) and 4-dimethylaminopyridine (31 mg) in CH2Cl2 (8 ml), pivaloylchloride (126 μl, 1.02 mmol) is added. After stirring for 14 h at RT, the mixture is diluted with CH2Cl2. The organic layer is washed with 1N HCl and saturated NaHCO3 solution, dried over Na2SO4 and evaporated in vacuo. The crude product is stirred with a solution of CH2Cl2/piperidine 4:1 (6 ml) for 1 h, the mixture is evaporated and the residue purified by preparative HPLC (YMC Pack Pro C18, 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA, 20 min, flow 20 ml/min). The combined pure fractions are treated with K2CO3, CH3CN is removed in vacuo, and the residual aqueous layer is extracted three times with CH2Cl2. The combined organic layers are dried (Na2SO4) and evaporated to afford the title compound as a yellowish resin. MS: 469.4 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, flow 1.5 ml/min): 5.03 min.

Workup

  1. additionis added
  2. washThe organic layer is washed with 1N HCl and saturated NaHCO3 solution
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo
  5. stirringThe crude product is stirred with a solution of CH2Cl2/piperidine 4:1 (6 ml) for 1 h
  6. customthe mixture is evaporated
  7. customthe residue purified by preparative HPLC (YMC Pack Pro C18, 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA, 20 min, flow 20 ml/min)
  8. additionThe combined pure fractions are treated with K2CO3, CH3CN
  9. customis removed in vacuo
  10. extractionthe residual aqueous layer is extracted three times with CH2Cl2
  11. dry with materialThe combined organic layers are dried (Na2SO4)
  12. customevaporated

Sources & evidence

ORD record
ord-23acce1f0a8e41c19d0088ad4c03a626
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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