1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 136377294, compound

HRID 1409327Notes

Reaction equation

HRID 1409327 reaction equation
[O:1]=[C:2]1[N:7]2[CH:8]=[C:9]([C:11]([OH:13])=O)[N:10]=[C:6]2[CH:5]=[CH:4][NH:3]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.[NH2:58][C@@H:59]([CH3:76])[CH2:60][N:61]1[CH:65]=[CH:64][C:63]([C:66]2[CH:73]=[C:72]([F:74])[C:69]([C:70]#[N:71])=[C:68]([Cl:75])[CH:67]=2)=[N:62]1>CN(C=O)C.CCOC(C)=O>[Cl:75][C:68]1[CH:67]=[C:66]([C:63]2[CH:64]=[CH:65][N:61]([CH2:60][C@@H:59]([NH:58][C:11]([C:9]3[N:10]=[C:6]4[CH:5]=[CH:4][NH:3][C:2](=[O:1])[N:7]4[CH:8]=3)=[O:13])[CH3:76])[N:62]=2)[CH:73]=[C:72]([F:74])[C:69]=1[C:70]#[N:71]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67170587(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile2×HCID 136304034HCID 136304034, compound

Product 1

HCID 136377294HCID 136377294, compoundYield 5.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

5-Oxo-5,6-dihydroimidazo[1,2-c]pyrimidine-2-carboxylic acid (0.323 mmol, 0.058 g), HBTU (0.027 mmol, 10.21 mg), DIPEA (0.323 mmol, 0.042 g) and EDCI (0.323 mmol, 0.062 g) were suspended in DMF (2 ml) and the resulting mixture was stirred at RT for 10 min. (S)-4-(1-(2-Aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile (0.269 mmol, 0.1 g) dissolved in DMF (2 ml) was added and the resulting mixture was stirred for 17 h at RT. At this point more starting materials were added so that the amount of every starting material was raised by half of the original amount. The amount of (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile was not changed. The reaction was continued for another 22 h after which the temperature was raised to 80° C. for 4.5 h. The reaction mixture was diluted with EtOAc and washed with 1M Na2CO3, brine and water. The organic phase was dried, filtered and evaporated. The crude product was purified by preparative HPLC. 0.006 g of the title compound was obtained. 1H-NMR (400 MHz, MeOH-d4): δ 1.25 (d, 3H), 4.30-4.37 (m, 1H), 4.42-4.49 (m, 1H), 4.54-4.65 (m, 1H), 6.61 (dd, 1H), 6.70 (d, 1H), 7.18 (d, 1H), 7.63 (d, 1H), 7.75-7.82 (m, 2H), 8.26 (s, 1H).

Workup

  1. additionwas added
  2. additionAt this point more starting materials were added so that the amount of every starting material
  3. temperaturewas raised by half of the original amount
  4. waitThe reaction was continued for another 22 h
  5. temperatureafter which the temperature was raised to 80° C. for 4.5 h
  6. washwashed with 1M Na2CO3, brine and water
  7. customThe organic phase was dried
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-1f102bc69014455ab67dac9f93329f4c
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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