Chlorotriethylsilane → HCID 131734779, compound

HRID 1777914Notes

Reaction equation

HRID 1777914 reaction equation
[NH2:1][C:2]1[CH:9]=[C:8]([NH:10][C@H:11]2[C@@H:16]([CH2:17][OH:18])[C@H:15]3[CH2:19][C@@H:12]2[CH2:13][CH2:14]3)[C:5]([C:6]#[N:7])=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.Cl[Si:30]([CH2:35][CH3:36])([CH2:33][CH3:34])[CH2:31][CH3:32]>C1COCC1>[NH2:1][C:2]1[CH:9]=[C:8]([NH:10][C@H:11]2[C@@H:16]([CH2:17][O:18][Si:30]([CH2:35][CH3:36])([CH2:33][CH3:34])[CH2:31][CH3:32])[C@H:15]3[CH2:19][C@@H:12]2[CH2:13][CH2:14]3)[C:5]([C:6]#[N:7])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 13819ChlorotriethylsilaneHCID 81531DiisopropylethylamineHCID 118036981HCID 118036981, compound2×

Product 1

HCID 131734779HCID 131734779, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Racemic 6-amino-4-(((1S*,2R*,3S*,4R*)-3-(hydroxymethyl)bicyclo[2.2.1]heptan-2-yl)amino)nicotinonitrile (intermediate 57, 420 mg, 1.63 mmol) was dissolved in THF (8 ml), treated with DIPEA (1.99 ml, 11.4 mmol) and chlorotriethylsilane (1.36 ml, 8.13 mmol). The reaction mixture was then stirred at 70° C. for 2 h. The reaction mixture was quenched with water and diluted in EtOAc. The org layer was separated, washed with water and brine, dried over Na2SO4, filtered and concentrated under vacuum. The crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) to give the title compound as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ 7.92 (s, 1H), 6.41 (s, 2H), 6.08 (d, 1H), 5.64 (s, 1H), 3.72 (d, 2H), 3.43 (t, 1H), 2.10-2.20 (m, 2H), 1.85-1.92 (m, 1H), 1.73 (d, 1H), 1.43-1.58 (m, 2H), 1.21 (t, 2H), 1.06 (d, 1H), 0.91 (t, 9H), 0.55-0.64 (m, 6H).

Workup

  1. customThe reaction mixture was quenched with water
  2. additiondiluted in EtOAc
  3. customThe org layer was separated
  4. washwashed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100)

Sources & evidence

ORD record
ord-9a602225fe684f6984eb783eddc86590
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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