Triethylsilane → (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)urea

HRID 590840Notes

Reaction equation

HRID 590840 reaction equation
[OH:1][C:2]([CH3:55])([CH3:54])[C@@H:3]([NH:10][C:11]([NH:13][C:14]1[CH:23]=[C:22]2[N:24](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:25]=[C:20]3[C:21]2=[C:16]([CH2:17][CH2:18][N:19]3CC2C=CC(OC)=CC=2)[N:15]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([SiH](CC)CC)C>C(O)(C(F)(F)F)=O>[OH:1][C:2]([CH3:55])([CH3:54])[C@@H:3]([NH:10][C:11]([NH:13][C:14]1[CH:23]=[C:22]2[NH:24][N:25]=[C:20]3[C:21]2=[C:16]([CH2:17][CH2:18][NH:19]3)[N:15]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 12052TriethylsilaneHCID 118381006(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(3-(4-methoxybenzyl)-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)urea

Product 1

HCID 136236930(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)urea

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(3-(4-methoxybenzyl)-1-trityl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)urea (38 mg, 0.052 mmol) was taken in TFA (0.17 mL) and stirred at room temperature for 30 minutes. To the reaction was added triethylsilane (34 uL, 0.209 mmol) stirred for 15 minutes at room temperature then heated to 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) gave (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)urea. MS ESI calc'd. for C19H22N6O2 [M+H]+ 367. found 367. 1H NMR (ppm, 500 MHz, DMSO-d6) δ 9.25 (br, 2H), 7.28 (m, 4H), 7.20 (m, 1H), 6.90 (s, 1H), 4.59 (d, J=14 Hz, 1H), 3.42 (dd, J=8.0, 5.0 Hz, 2H), 2.92 (dd, J=8.0, 5.0 Hz, 2H), 1.95 (s, 3H), 1.0 (s, 3H).

Workup

  1. stirringstirred for 15 minutes at room temperature
  2. temperaturethen heated to 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)

Sources & evidence

ORD record
ord-627ebd0a9f6e4998ae822930724840fe
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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