Dimethylformamide → HCID 67497612, compound

HRID 1628205Notes

Reaction equation

HRID 1628205 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[S:8]C(N)=[CH:10][N:11]=2)=[CH:3][CH:2]=1.[C:13]([O:17][C:18]([C@@H](CC1C=CC(F)=CC=1)C(O)=O)=[O:19])([CH3:16])([CH3:15])[CH3:14].CN(C(ON1N=N[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]1=2)=[N+](C)C)C.[F:49][P-](F)(F)(F)(F)F.[CH2:56]([N:58](C(C)C)C(C)C)[CH3:57].[CH3:65][N:66](C)[CH:67]=[O:68]>O>[F:49][C:41]1[CH:42]=[CH:43][C:44]([CH2:57][C@H:56]([NH:58][C:18](=[O:19])[O:17][C:13]([CH3:14])([CH3:15])[CH3:16])[C:67](=[O:68])[NH:66][C:65]2[S:8][C:7]([C:4]3[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=3)=[N:11][CH:10]=2)=[CH:45][CH:46]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45788714HCID 45788714, compoundHCID 67496682HCID 67496682, compound

Product 1

HCID 67497612HCID 67497612, compoundYield 10.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(pyridin-4-yl)thiazol-5-amine (0.987 g, 5.57 mmol), (S)-2-(tert-butoxycarbonyl)-3-(4-fluorophenyl)propanoic acid (1.58 g, 5.57 mmol), HBTU (2.11 g, 5.57 mmol) and N-ethyl-N-isopropylpropan-2-amine (2.43 ml, 13.9 mmol) in N,N-dimethylformamide (11.1 ml, 5.57 mmol) was allowed to stir at 80° C. for 4 hours. 20 mL of water was added and the resulting mixture was extracted with DCM (40 mL×4). The extract was dried and concentrated. The residue was purified by CombiFlash using 0-10% methanol/DCM to give 250 mg of (S)-tert-butyl 3-(4-fluorophenyl)-1-oxo-1-(2-(pyridin-4-yl)thiazol-5-ylamino)propan-2-ylcarbamate 5.2A. 400 MHz 1H NMR (CD3OD) δ: 8.78 (d, 2H), 8.43 (d, J=8.0 Hz, 2H), 7.87 (s, 1H), 7.27 (dd, J=8.0, 4.0 Hz, 2H), 7.01 (dd, 2H), 4.50 (m, 1H), 3.15 (m, 1H), 2.99 (m, 1H), 1.40 (s, 9H). LCMS (ES+) m/z 443.

Workup

  1. extractionthe resulting mixture was extracted with DCM (40 mL×4)
  2. customThe extract was dried
  3. concentrationconcentrated
  4. customThe residue was purified by CombiFlash

Sources & evidence

ORD record
ord-c5ae657eb5f44a5fb78d977bcc45be2f
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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