Triphenylphosphine → tert-butyl 4-[8-[[(2S)-1-benzylpyrrolidin-2-yl]methyl-tert-butoxycarbonyl-sulfamoyl]-5,8-diazaspiro[2.5]octan-5-yl]pyrrolo[2,3-d]pyrimidine-7-carboxylate

HRID 589960Notes

Reaction equation

HRID 589960 reaction equation
[C:1]([O:5][C:6]([NH:8][S:9]([N:12]1[C:17]2([CH2:19][CH2:18]2)[CH2:16][N:15]([C:20]2[C:21]3[CH:28]=[CH:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:22]=3[N:23]=[CH:24][N:25]=2)[CH2:14][CH2:13]1)(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:36]([N:43]1[CH2:47][CH2:46][CH2:45][C@H:44]1[CH2:48]O)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(/N=N\C(=O)OC(C)C)=O)(C)C>C1COCC1.O>[CH2:36]([N:43]1[CH2:47][CH2:46][CH2:45][C@H:44]1[CH2:48][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[S:9]([N:12]1[C:17]2([CH2:18][CH2:19]2)[CH2:16][N:15]([C:20]2[C:21]3[CH:28]=[CH:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:22]=3[N:23]=[CH:24][N:25]=2)[CH2:14][CH2:13]1)(=[O:11])=[O:10])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 719760[(2S)-1-benzylpyrrolidin-2-yl]methanolHCID 567765201-Diazene-1,2-dicarboxylic acid, 1,2-bis(1-methylethyl) ester, (1Z)-HCID 68295965Tert-butyl 4-[8-(tert-butoxycarbonylsulfamoyl)-5,8-diazaspiro[2.5]octan-5-yl]pyrrolo[2,3-d]pyrimidine-7-carboxylate2×

Product 1

HCID 68296033tert-butyl 4-[8-[[(2S)-1-benzylpyrrolidin-2-yl]methyl-tert-butoxycarbonyl-sulfamoyl]-5,8-diazaspiro[2.5]octan-5-yl]pyrrolo[2,3-d]pyrimidine-7-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Tert-butyl 4-[8-(tert-butoxycarbonylsulfamoyl)-5,8-diazaspiro[2.5]octan-5-yl]pyrrolo[2,3-d]pyrimidine-7-carboxylate (intermediate 47) (0.55 mmol) was dissolved in dry THF (3 mL) and added [(2S)-1-benzylpyrrolidin-2-yl]methanol (0.61 mmol) and triphenylphosphine (0.66 mmol). The reaction mixture was cooled to 0° C. and slowly added isopropyl (NZ)—N-isopropoxycarbonyliminocarbamate (0.66 mmol). The reaction mixture was allowed to warm up freely to rt and stirred at rt for 16 h. The crude mixture was treated with water (50 mL) and extracted with EtOAc (3×50 mL). The combined organic phases were washed with H2O (2×50 mL), brine (2×50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The product was purified by flash chromatography on silica using EtOAc in heptane as eluent.

Workup

  1. temperatureto warm up freely to rt
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined organic phases were washed with H2O (2×50 mL), brine (2×50 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by flash chromatography on silica

Sources & evidence

ORD record
ord-53dad9186c7f47899c57695be0a77be8
Source dataset
uspto-grants-2016_01
Patent number
US09233964B2

Reaction notes

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