Dimethylformamide → HCID 58958459, compound

HRID 915171Notes

Reaction equation

HRID 915171 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[S:11][C:10]([NH:12][Si](C)(C)C)=[N:9][CH:8]=2)=[O:6])[CH2:3][CH2:2]1.C(Cl)(Cl)=O.CC[N:23](C(C)C)[CH:24]([CH3:26])[CH3:25].[CH3:30][N:31]([CH:33]=[O:34])[CH3:32]>C1(C)C=CC=CC=1.C(Cl)Cl>[NH2:23][CH:24]1[CH2:26][CH2:32][N:31]([C:33]([NH:12][C:10]2[S:11][C:7]([C:5]([NH:4][CH:1]3[CH2:3][CH2:2]3)=[O:6])=[CH:8][N:9]=2)=[O:34])[CH2:30][CH2:25]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 58958442HCID 58958442, compound

Product 1

HCID 58958459HCID 58958459, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

N-Cyclopropyl-2-[(trimethylsilyl)amino]-1,3-thiazole-5-carboxamide 23-5 (0.26 g, 1.0 mmol) was treated with 2 mL of phosgene (as a 20% solution in toluene) and 1 mL of methylene chloride at room temperature for 4 hours. The suspension was concentrated to dryness and the residue was treated with a suspension of DIEA (0.16 g, 1.2 mmol) and 4-boc-amino-1-piperidine 23-6 (0.20 g, 1.0 mmol) in 1 mL of dry DMF and 1 mL of methylene chloride overnight at room temperature. The intermediate product was purified on C18 column and the residue treated with TFA. The crude product was purified on a C18 preparative HPLC column and isolated via lyophilization to afford the final product 23-7. Hi-Res MS: calc: 310.1332 found: 310.1334. 1H-NMR (DMSO): 8.33 ppm (s, 1H); 7.92 ppm (s, 1H); 7.84 ppm (m, 3H); 3.27 ppm (m, 1H); 2.91 ppm (t, 2H); 2.75 ppm (m, 1H); 1.90 ppm (d, 2H); 1.40 ppm (q, 2H); 0.67 ppm (m, 2H); 0.52 ppm (m, 2H).

Workup

  1. concentrationThe suspension was concentrated to dryness
  2. customThe intermediate product was purified on C18 column
  3. additionthe residue treated with TFA
  4. customThe crude product was purified on a C18 preparative HPLC column
  5. customisolated via lyophilization

Sources & evidence

ORD record
ord-2fca7136c2e54a6b8b42947d1913b9af
Source dataset
uspto-grants-2007_09
Patent number
US07265134B2

Reaction notes

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