Sodium Bicarbonate → (S)-2-benzyl 3-ethyl 8-(6-(adamantan-1-ylmethoxy)-2-aminopyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

HRID 1499206Notes

Reaction equation

HRID 1499206 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[CH:18]=[C:17](Cl)[N:16]=[C:15]([NH2:20])[N:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH2:21]1[C:25]2([CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH2:24][C@@H:23]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[N:22]1[C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:37].C([O-])(O)=O.[Na+]>O1CCOCC1>[C:1]12([CH2:11][O:12][C:13]3[N:14]=[C:15]([NH2:20])[N:16]=[C:17]([N:28]4[CH2:27][CH2:26][C:25]5([CH2:21][N:22]([C:36]([O:38][CH2:39][C:40]6[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=6)=[O:37])[C@H:23]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:24]5)[CH2:30][CH2:29]4)[CH:18]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 1179417652-Benzyl 3-ethyl (3S)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylateHCID 1179420184-(Adamantan-1-ylmethoxy)-6-chloro-pyrimidin-2-ylamine

Product 1

HCID 117941859(S)-2-benzyl 3-ethyl 8-(6-(adamantan-1-ylmethoxy)-2-aminopyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

4-(Adamantan-1-ylmethoxy)-6-chloro-pyrimidin-2-ylamine (89 mg, 0.30 mmol), (S)-2-benzyl 3-ethyl 2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (157 mg, 0.45 mmol) and NaHCO3 (76 mg, 0.9 mmol) were dissolved in dioxane (1.5 mL) and heated to 95° C. for 64 h. Then the reaction was cooled to RT, quenched with water, and extracted with EtOAc. The organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase silica gel column (EtOAc/heptane) provides (S)-2-benzyl 3-ethyl 8-(6-(adamantan-1-ylmethoxy)-2-aminopyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid.

Workup

  1. temperatureThen the reaction was cooled to RT
  2. customquenched with water
  3. extractionextracted with EtOAc
  4. washThe organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by normal phase silica gel column (EtOAc/heptane)

Sources & evidence

ORD record
ord-fffc1eb73a1e47408733c8c38a47e0ce
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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