Diisopropylethylamine → HCID 86723631, compound

HRID 1485296Notes

Reaction equation

HRID 1485296 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]4[CH2:27][CH2:26][CH2:25][C:12]=4[N:13]=[C:14]([N:16]4[CH2:20][CH2:19][CH2:18][C@@:17]4([CH3:24])[C:21](O)=[O:22])[N:15]=3)[CH:5]=2)[CH2:3][CH2:2]1.[F:28][C:29]1[N:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]4[CH2:27][CH2:26][CH2:25][C:12]=4[N:13]=[C:14]([N:16]4[CH2:20][CH2:19][CH2:18][C@@:17]4([CH3:24])[C:21]([NH:35][C:32]4[CH:33]=[N:34][C:29]([F:28])=[CH:30][CH:31]=4)=[O:22])[N:15]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 8194405-Amino-2-fluoropyridineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86723632HCID 86723632, compound

Product 1

HCID 86723631HCID 86723631, compoundYield 3.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methylpyrrolidine-2-carboxylic acid (1.1 g, 2.99 mmol) in DMF (12 mL) was added 6-fluoropyridin-3-amine (1.7 g, 15.18 mmol), diisopropylethylamine (0.578 g, 4.48 mmol) and HBTU (1.13 g, 2.99 mmol) and the reaction mixture was stirred at RT for 16 h. The reaction mixture was diluted with water (200 mL) and extracted with EtOAc (3×100 mL). The combined organic layer was washed with water (9×200 mL) and dried over anhydrous sodium sulfate. Removal of solvent under reduced pressure gave a crude product which was purified by reverse phase HPLC to afford 50 mg of (S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide. 1H NMR (400 MHz, CD3OD, TFA salt) δ (ppm): 0.70-0.80 (m, 2H), 0.89-0.99 (m, 2H), 1.77-1.83 (m, 1H), 1.80 (s, 3H), 2.16-2.30 (m, 5H), 2.38-2.43 (m, 1H), 2.77-2.83 (m, 2H), 2.98-3.05 (m, 2H), 3.78-3.82 (m, 1H), 3.88-3.98 (m, 1H), 6.02 (s, 1H), 6.99 (d, 1H), 7.82-7.90 (m, 1H), 8.18 (s, 1H). The other enantiomer was prepared using the (R) chiral starting material.

Workup

  1. extractionextracted with EtOAc (3×100 mL)
  2. washThe combined organic layer was washed with water (9×200 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customRemoval of solvent under reduced pressure
  5. customgave a crude product which
  6. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-15acdf9983d143e4a2105a864c945aa6
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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