Diisopropylethylamine → HCID 86723640, compound

HRID 1485304Notes

Reaction equation

HRID 1485304 reaction equation
[CH:1]1([C:4]2[CH:8]=[C:7]([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][CH:19]([OH:21])[CH2:18][CH:17]4[C:22](O)=[O:23])[N:15]=3)[NH:6][N: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.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.CCOC(C)=O>[CH:1]1([C:4]2[NH:5][N:6]=[C:7]([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][C@H:19]([OH:21])[CH2:18][C@H:17]4[C:22]([NH:35][C:32]4[CH:33]=[N:34][C:29]([F:28])=[CH:30][CH:31]=4)=[O:23])[N:15]=3)[CH:8]=2)[CH2:2][CH2:3]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 178524619HCID 178524619, compound

Product 1

HCID 86723640HCID 86723640, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(4-(3-cyclopropyl-1H-pyrazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-hydroxypyrrolidine-2-carboxylic acid (200 mg, 0.54 mmol) in DMF (3 mL) was added 6-fluoropyridin-3-amine (121 mg, 1.08 mmol), HATU (246 mg, 0.648 mmol) and DIPEA (0.16 mL, 0.864 mmol). The reaction mixture was allowed to stir at RT for 16 h. The reaction mixture was diluted with EtOAc (50 mL), washed with water (4×25 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 (2S,4R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-hydroxypyrrolidine-2-carboxamide (10 mg). Compound No. 10a: 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 0.60-0.68 (m, 2H), 0.80-0.92 (m, 2H), 1.71-1.81 (m, 1H), 1.90-2.01 (m, 1H), 2.03-2.17 (m, 2H), 2.30-2.41 (m, 2H), 2.65-2.83 (m, 4H), 3.75-3.91 (m, 2H), 4.51-4.60 (m, 1H), 6.07 (s, 1H), 6.97 (d, 1H), 7.99 (s, 1H), 8.19 (s, 1H). Compound No. 10b: 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 0.60-0.68 (m, 2H), 0.80-0.92 (m, 2H), 1.71-1.81 (m, 1H), 1.90-2.01 (m, 1H), 2.03-2.17 (m, 2H), 2.30-2.41 (m, 2H), 2.65-2.83 (m, 4H), 3.75-3.91 (m, 2H), 4.51-4.60 (m, 1H), 6.07 (s, 1H), 6.97 (d, 1H), 7.99 (s, 1H), 8.19 (s, 1H). Separation by chiral HPLC provided additional diastereomers 10c and 10d.

Workup

  1. washwashed with water (4×25 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. customRemoval of EtOAc under reduced pressure
  4. customgave a crude product that
  5. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-b690e89d573f41b19333631ed21b2b13
Source dataset
uspto-grants-2016_08
Patent number
US09422267B2

Reaction notes

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