Triethylsilane → 1-((R)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea

HRID 590844Notes

Reaction equation

HRID 590844 reaction equation
COC1C=CC(C[N:8]2[CH:17]([CH3:18])[CH2:16][C:15]3[N:14]=[C:13]([NH:19][C:20]([NH:22][C@@H:23]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:24])=[O:21])[CH:12]=[C:11]4[NH:31][N:32]=[C:9]2[C:10]=34)=CC=1.C([SiH](CC)CC)C>C(O)(C(F)(F)F)=O>[CH3:18][C@@H:17]1[CH2:16][C:15]2[N:14]=[C:13]([NH:19][C:20]([NH:22][C@@H:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH3:24])=[O:21])[CH:12]=[C:11]3[NH:31][N:32]=[C:9]([C:10]=23)[NH:8]1

Participants

4

Reactant 2

HCID 12052TriethylsilaneHCID 1182719941-(3-(4-methoxybenzyl)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea

Product 1

HCID 1362369311-((R)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

1-(3-(4-methoxybenzyl)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea (100 mg, 0.143 mmol) was taken in TFA (0.7 mL) and stirred at room temperature for 30 minutes. Triethylsilane (91 uL, 0.572 mmol) was added to the reaction mixture and stirred for 15 minutes at room temperature then heated at 80° C. for 30 minutes. The reaction mixture was concentrated, taken in DCM and washed with aqueous sodium bicarbonate, brine, dried with sodium sulfate and concentrated. Purification of the residue by flash column (0-15% MeOH-DCM) followed by SFC separation with a Chiralpak AS-H column gave 1-((R)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea as peak 1. MS ESI calc'd. for C18H20N6O [M+H]+ 337. found 337. 1H NMR (ppm, 500 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.90 (s, 1H), 8.40 (br, s, 1H), 7.32 (dd, J=3.4, 7.9, 4H), 7.24-7.14 (m, 1H), 7.00 (s, 1H), 6.30 (s, 1H), 4.83 (m, 1H), 3.65 (m, 1H), 2.88-2.77 (m, 1H), 2.67-2.53 (m, 1H), 1.39 (d, J=6.9, 3H), 1.29 (d, J=6.3, 3H).

Workup

  1. stirringstirred for 15 minutes at room temperature
  2. temperaturethen heated at 80° C. for 30 minutes
  3. concentrationThe reaction mixture was concentrated
  4. washwashed with aqueous sodium bicarbonate, brine
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated
  7. customPurification of the residue by flash column (0-15% MeOH-DCM)
  8. customfollowed by SFC separation with a Chiralpak AS-H column

Sources & evidence

ORD record
ord-a1671c2c2e5d457b8495ae482e5a3a70
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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