1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86714624, compound

HRID 1409306Notes

Reaction equation

HRID 1409306 reaction equation
[OH:1][C:2]([C:5]1[O:6][CH:7]=[C:8](C(O)=O)[N:9]=1)([CH3:4])[CH3:3].CCN=C=NCCCN(C)C.CC[N:26]([CH:30]([CH3:32])[CH3:31])[CH:27](C)C.C1C=CC2N([OH:42])N=NC=2C=1.N[C@@H](C)C[N:46]1[CH:50]=[CH:49][C:48]([C:51]2[CH:58]=[C:57]([F:59])[C:54]([C:55]#[N:56])=[C:53]([Cl:60])[C:52]=2[F:61])=[N:47]1>CN(C=O)C.O.CCOC(C)=O>[Cl:60][C:53]1[C:52]([F:61])=[C:51]([C:48]2[CH:49]=[CH:50][N:46]([CH2:32][C@@H:30]([NH:26][C:27]([C:7]3[O:6][C:5]([C:2]([OH:1])([CH3:3])[CH3:4])=[N:9][CH:8]=3)=[O:42])[CH3:31])[N:47]=2)[CH:58]=[C:57]([F:59])[C:54]=1[C:55]#[N:56]

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67169360HCID 67169360, compoundHCID 86714622HCID 86714622, compound

Product 1

HCID 86714624HCID 86714624, compoundYield 61.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-(2-Hydroxypropan-2-yl)oxazole-4-carboxylic acid (0.514 mmol, 0.088 g) was dissolved in DMF (10 ml) under nitrogen atmosphere. EDCI (0.514 mmol, 0.098 g), DIPEA (0.856 mmol, 0.111 g) and HOBt (0.214 mmol, 0.029 g) were added and the resulting mixture was stirred for 20 min at RT. (S)-4-(1-(2-amino-propyl)-1H-pyrazol-3-yl)-2-chloro-3,6-difluorobenzonitrile (0.428 mmol, 0.127 g) dissolved in DMF (5 ml) was added and the resulting mixture was stirred at RT for 3 days. The mixture was diluted with water and EtOAc, washed with 2 M Na2CO3, water and brine. The combined organics were dried, filtered and evaporated. The crude product was purified by flash chromatography. 0.059 g of the title compound was obtained. 1H-NMR (400 MHz, MeOH-d4): δ 1.26 (d, 3H), 1.61 (s, 6H), 4.34-4.46 (m, 2H), 4.54-4.63 (m, 1H), 6.78-6.82 (m, 1H), 7.76 (d, 1H), 7.87-7.93 (m, 1H), 8.24 (s, 1H).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at RT for 3 days
  3. washwashed with 2 M Na2CO3, water and brine
  4. customThe combined organics were dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-5378c09dcfc747f4ac77e5c2f9e23d66
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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