Diisopropylethylamine → HCID 90024952, compound

HRID 1057031Notes

Reaction equation

HRID 1057031 reaction equation
OC(C(F)(F)F)=O.[CH3:8][C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][N:23]=2)[C:19]#[N:20])[CH:12]=[C:11]([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH:10]=1.C(N(CC)C(C)C)(C)C.[O:39]1[CH2:42][C:41](=O)[CH2:40]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C(Cl)Cl>[CH3:8][C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][N:23]=2)[C:19]#[N:20])[CH:12]=[C:11]([CH:24]2[CH2:29][CH2:28][N:27]([CH:41]3[CH2:42][O:39][CH2:40]3)[CH2:26][CH2:25]2)[CH:10]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 131736452HCID 131736452, compound

Product 1

HCID 90024952HCID 90024952, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 2-((6-methyl-4-(piperidin-4-yl)pyridin-2-yl)amino)isonicotinonitrile mono-TFA salt (33.8 mg, 0.0830 mmol) in anhydrous THF (0.8 mL) was added N,N-diisopropylethylamine (24 μL, 0.17 mmol) followed by 3-oxetanone (8.0 μL, 0.12 mmol) and the mixture was stirred for 15 min before the introduction of sodium triacetoxyborohydride (55 mg, 0.25 mmol). After stirring for a further 17 hr, the mixture was diluted with CH2Cl2 and washed with sat. aq. NaHCO3 and the organics were dried over MgSO4 and concentrated to dryness. The residue thus obtained was purified by RPLC to afford 2-((6-methyl-4-(1-(oxetan-3-yl)piperidin-4-yl)pyridin-2-yl)amino)isonicotinonitrile as a colorless solid (9.5 mg, 34%); 1H NMR (400 MHz, DMSO) δ 9.99 (br s, 1H), 8.44 (d, J=5.1 Hz, 1H), 8.18 (s, 1H), 7.36 (s, 1H), 7.21 (d, J=5.1 Hz, 1H), 6.75 (s, 1H), 4.54 (dd, J=6.5, 6.5 Hz, 2H), 4.45 (dd, J=6.5, 6.5 Hz, 2H), 3.42 (m, 1H), 2.80 (m, 2H), 2.44 (m, 1H), 2.40 (s, 3H), 1.86 (m, 2H), 1.76 (m, 2H), 1.63 (m, 2H); ESI-LRMS m/z [M+1]+=350.

Workup

  1. washwashed with sat. aq. NaHCO3
  2. dry with materialthe organics were dried over MgSO4
  3. concentrationconcentrated to dryness
  4. customThe residue thus obtained
  5. customwas purified by RPLC

Sources & evidence

ORD record
ord-ca8171e67d4e49d594b55f2153a0e5f7
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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