Diisopropylethylamine → HCID 178521020, compound

HRID 931291Notes

Reaction equation

HRID 931291 reaction equation
[F:1][C:2]1([F:6])[CH2:5][NH:4][CH2:3]1.[Cl:7][C:8]1[CH:9]=[N:10][N:11]([C:13]2([C:16]3[NH:33][C:19]4=[N:20][C:21]([N:24]5[CH2:29][CH2:28][CH2:27][C@@H:26]([C:30](O)=[O:31])[CH2:25]5)=[CH:22][CH:23]=[C:18]4[N:17]=3)[CH2:15][CH2:14]2)[CH:12]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>ClCCl>[Cl:7][C:8]1[CH:9]=[N:10][N:11]([C:13]2([C:16]3[NH:33][C:19]4=[N:20][C:21]([N:24]5[CH2:29][CH2:28][CH2:27][C@@H:26]([C:30]([N:4]6[CH2:5][C:2]([F:6])([F:1])[CH2:3]6)=[O:31])[CH2:25]5)=[CH:22][CH:23]=[C:18]4[N:17]=3)[CH2:15][CH2:14]2)[CH:12]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27582483,3-DifluoroazetidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178525787HCID 178525787, compound

Product 1

HCID 178521020HCID 178521020, compoundYield 43.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3,3-Difluoroazetidine (33 mg, 0.2 mmol) was added to a mixture of (R)-1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylic acid (100 mg, 0.25 mmol), diisopropylethylamine (0.1 mL, 0.77 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′,-tetramethyluronium hexafluorophosphate (HATU) (118 mg, 0.31 mmol) in anhydrous dichloromethane (5 mL) at room temperature. The reaction mixture was stirred for 2 h, then partitioned between dichloromethane and water. The organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via preparative TLC to afford the title compound (40 mg, 43% yield). MS (ES+) (M+H) 462.2; LCMS retention time 2.163 minutes (Method N1). 1H NMR (300 MHz, CDCl3) δ 1.17-1.39 (m, 1H), 1.71-2.24 (m, 7H), 2.35-2.58 (m, 1H), 2.83-3.13 (m, 2H), 4.04-4.78 (m, 6H), 6.63 (d, 1H), 7.62 (s, 2H), 7.69-7.80 (m, 1H), 9.15 (br s, 1H).

Workup

  1. custompartitioned between dichloromethane and water
  2. dry with materialThe organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified via preparative TLC

Sources & evidence

ORD record
ord-044775a57c664b9392b07addf661403b
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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