Water → HCID 58299982, compound

HRID 875960Notes

Reaction equation

HRID 875960 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([N:22]5[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]5)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:28]=[CH:29][N:30]=[CH:31][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.O.C(O[C:36]1(O[Si](C)(C)C)[CH2:38][CH2:37]1)C.C([BH3-])#N.[Na+]>C1COCC1.C(O)(=O)C>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([N:22]5[CH2:27][CH2:26][N:25]([CH:36]6[CH2:38][CH2:37]6)[CH2:24][CH2:23]5)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:28]=[CH:29][N:30]=[CH:31][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 962WaterHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 441325859-Cyclopentyl-N-(5-Piperazin-1-Ylpyridin-2-Yl)pyrido[4,5]pyrrolo[1,2-D]pyrimidin-2-Amine

Product 1

HCID 58299982HCID 58299982, compoundYield 26.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of compound 7 (207 mg, 0.50 mmol) in THF (5 mL) were added water (0.05 mL), (1-ethoxy-1-cyclopropyloxy)-trimethylsilane (1174 mg, 1.0 mmol), acetic acid (0.55 mL) and sodium cyanoborohydride (1 mL, 1 M in THF, 1.0 mmol). The mixture was stirred at 60° C. overnight. The reaction mixture was concentrated and the residue was dissolved in ethyl acetate and washed with saturated NaHCO3 and brine then dried. The solvent was evaporated and the residue was purified by chromatography on silica gel eluting with CH2Cl2:methanol:NH4OH (400:10:1) to give compound 187 as a yellow solid (60 mg, 26% yield). 1H NMR (500 MHz, CDCl3) δ 9.08 (1H, s), 8.90 (1H, s), 8.51 (1 H, d, J=5 Hz), 8.39 (1H, d, J=10 Hz), 8.18 (1H, bs), 8.07 (1H, d, J=2 Hz), 7.84 (1H, d, J=5 Hz), 7.39 (1H, dd, J=10 Hz, J=2 Hz), 5.38 (1H, p, J=10 Hz), 3.17 (4H, q, J=5 Hz), 2.83 (2H, t, J=5 Hz), 2.42 (2H, m), 2.21-2.14 (4H, m), 1.88 (2H, m), 1.71 (1H, m), 0.53-0.46 (4H, m) ppm; LCMS-ESI (POS), M/Z, M+1: Found 454.2, Calculated 454.3.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed with saturated NaHCO3 and brine
  4. customthen dried
  5. customThe solvent was evaporated
  6. customthe residue was purified by chromatography on silica gel eluting with CH2Cl2:methanol:NH4OH (400:10:1)

Sources & evidence

ORD record
ord-00f1824f46ba4a739e09c527fed7bf05
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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