Diisopropylethylamine → HCID 178522406, compound

HRID 1485301Notes

Reaction equation

HRID 1485301 reaction equation
[CH:1]1([C:4]2[CH:8]=[C:7]([NH:9][C:10]3[C:11]4[CH2:26][CH2:25][CH2:24][C:12]=4[N:13]=[C:14]([N:16]4[CH2:20][CH2:19][CH2:18][CH:17]4[C:21](O)=[O:22])[N:15]=3)[NH:6][N:5]=2)[CH2:3][CH2:2]1.[N:27]1[CH:32]=[C:31]([NH2:33])[CH:30]=[N:29][CH:28]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH:1]1([C:4]2[CH:8]=[C:7]([NH:9][C:10]3[C:11]4[CH2:26][CH2:25][CH2:24][C:12]=4[N:13]=[C:14]([N:16]4[CH2:20][CH2:19][CH2:18][CH:17]4[C:21]([NH:33][C:31]4[CH:32]=[N:27][CH:28]=[N:29][CH:30]=4)=[O:22])[N:15]=3)[NH:6][N:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 344373Pyrimidin-5-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178524416HCID 178524416, compound

Product 1

HCID 178522406HCID 178522406, compoundYield 3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-(3-cyclopropyl-1H-pyrazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylic acid (300 mg, 0.847 mmol) in DMF (4 mL) was added pyrimidin-5-amine (201 mg, 2.11 mmol), HATU (386 mg, 1.016 mmol) and DIPEA (0.24 mL, 1.4 mmol). The reaction mixture was allowed to stir at RT for 16 h. The reaction mixture was diluted with water (40 mL) and extracted with EtOAc (2×25 mL). The organic layer was washed with water (8×30 mL) and dried over anhydrous sodium sulfate. Removal of EtOAc under reduced pressure gave a crude product that was purified by reverse phase HPLC to afford 11 mg of 1-(4-(3-cyclopropyl-1H-pyrazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrimidin-5-yl)pyrrolidine-2-carboxamide as free base. 1H NMR (400 MHz, CD3OD, formate salt) δ (ppm): 0.58-0.67 (m, 2H), 0.80-0.94 (m, 2H), 1.70-1.78 (m, 1H), 2.09-2.21 (m, 4H), 2.22-2.42 (m, 2H), 2.78-2.81 (m, 2H), 2.82-2.95 (m, 2H), 3.60-2.70 (m, 1H), 3.78-3.88 (m, 1H), 4.78 (dd, 1H), 6.08 (s, 1H), 8.84 (s, 1H), 8.89 (s, 2H). Separation by chiral HPLC provided enantiomers 7a and 7b.

Workup

  1. extractionextracted with EtOAc (2×25 mL)
  2. washThe organic layer was washed with water (8×30 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customRemoval of EtOAc under reduced pressure
  5. customgave a crude product that
  6. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-54615688604249548ca1b81746094979
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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