1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-7-oxo-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carboxamide

HRID 1409316Notes

Reaction equation

HRID 1409316 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][N:5]2[CH:8]=[C:9]([C:11]([OH:13])=O)[N:10]=[C:4]2[NH:3]1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:44][C@@H:45]([CH3:62])[CH2:46][N:47]1[CH:51]=[CH:50][C:49]([C:52]2[CH:59]=[C:58]([F:60])[C:55]([C:56]#[N:57])=[C:54]([Cl:61])[CH:53]=2)=[N:48]1>CN(C=O)C.O.CCOC(C)=O>[Cl:61][C:54]1[CH:53]=[C:52]([C:49]2[CH:50]=[CH:51][N:47]([CH2:46][C@@H:45]([NH:44][C:11]([C:9]3[N:10]=[C:4]4[NH:3][C:2](=[O:1])[CH2:7][CH2:6][N:5]4[CH:8]=3)=[O:13])[CH3:62])[N:48]=2)[CH:59]=[C:58]([F:60])[C:55]=1[C:56]#[N:57]

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67170587(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrileHCID 1363772927-Oxo-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carboxylic acid

Product 1

HCID 136216928(S)-N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-7-oxo-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carboxamideYield 1.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

7-Oxo-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carboxylic acid (1.513 mmol, 0.274 g) was dissolved in DMF (5 ml) under nitrogen atmosphere. EDCI (1.891 mmol, 0.362 g), DIPEA (3.78 mmol, 0.489 g) and HOBt (1.891 mmol, 0.255 g) were added and the resulting mixture was stirred for 20 min at RT. (S)-4-(1-(2-Aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile (1.260 mmol, 0.351 g) dissolved in DMF (5 ml) was added and the resulting mixture was stirred at RT for 2 days. The mixture was diluted with water and EtOAc, washed with 2M Na2CO3, water and brine. The combined organics were dried, filtered and evaporated. The crude product was purified by preparative HPLC. 0.0089 g of the title compound was obtained. 1H-NMR (400 MHz, CDCl3): δ 1.28 (d, 3H), 2.89 (t, 2H), 4.16 (t, 2H), 4.33-4.39 (m, 2H), 4.54-4.65 (m, 1H), 6.59 (d, 1H), 7.36 (s, 1H), 7.53 (d, 1H), 7.57 (dd, 1H), 7.72-7.75 (m, 1H), 7.83 (d, 1H).

Workup

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

Sources & evidence

ORD record
ord-0d3d87d483df4e1485690c1c0d2c8f20
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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