Diisopropylethylamine → HCID 86723637, compound

HRID 1485299Notes

Reaction equation

HRID 1485299 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]4[CH2:25][CH2:24][CH2:23][C:12]=4[N:13]=[C:14]([N:16]4[CH2:19][CH2:18][C@H:17]4[C:20]([OH:22])=O)[N:15]=3)[CH:5]=2)[CH2:3][CH2:2]1.[F:26][C:27]1[N:32]=[CH:31][C:30]([NH2:33])=[CH: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[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]4[CH2:25][CH2:24][CH2:23][C:12]=4[N:13]=[C:14]([N:16]4[CH2:19][CH2:18][C@H:17]4[C:20]([NH:33][C:30]4[CH:31]=[N:32][C:27]([F:26])=[CH:28][CH:29]=4)=[O:22])[N:15]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 8194405-Amino-2-fluoropyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86723638HCID 86723638, compound

Product 1

HCID 86723637HCID 86723637, compoundYield 10.1%

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)azetidine-2-carboxylic acid (300 mg, 0.909 mmol) in DMF (3 mL) was added 6-fluoropyridin-3-amine (203 mg, 1.818 mmol), HATU (414 mg, 1.091 mmol) and DIPEA (0.26 mL, 1.45 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 40 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)azetidine-2-carboxamide as the formate salt. 1H NMR (400 MHz, CD3OD, TFA salt) δ (ppm): 0.40-0.60 (m, 2H), 0.70-0.85 (m, 2H), 1.58-1.70 (m, 1H), 2.20-2.37 (m, 2H), 2.58-2.69 (m, 1H), 2.79-2.97 (m, 3H), 2.98-3.06 (m, 2H), 4.21-4.38 (2H), 5.16 (dd, 1H), 6.16 (s, 1H), 7.05 (dd, 1H), 8.05-8.17 (m, 1H), 8.30 (s, 1H). The other enantiomer was prepared using the (R) chiral starting material.

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-e0bceeb01c974c91980da22627dc2b30
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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