5-(chloromethyl)-1-cyclopropyl-1H-1,2,3,4-tetrazole → (2S,3S)-1-[5-tert-Butyl-2-(1-cyclopropyl-1H-tetrazol-5-ylmethyl)-2H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl]-2-hydroxymethyl-pyrrolidin-3-ol

HRID 2179087Notes

Reaction equation

HRID 2179087 reaction equation
[C:1]([C:5]1N=C(N2CCC(F)(F)C2)[C:8]2[C:9](=[N:11][N:12](CC)[N:13]=2)[N:10]=1)([CH3:4])(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][CH2:39][C@H:38]([O:41]C(=O)C(F)(F)F)[C@@H:37]2[CH2:48][O:49]C(=O)C(F)(F)F)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].ClCC1N(C2CC2)N=NN=1>CO>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][CH2:39][C@H:38]([OH:41])[C@@H:37]2[CH2:48][OH:49])[C:30]2[C:31](=[N:33][N:34]([CH2:8][C:9]3[N:10]([CH:5]4[CH2:1][CH2:4]4)[N:13]=[N:12][N:11]=3)[N:35]=2)[N:32]=1)([CH3:24])([CH3:25])[CH3:26]

Participants

5

Reactant 3

HCID 255244995-(chloromethyl)-1-cyclopropyl-1H-1,2,3,4-tetrazoleHCID 715763075-tert-Butyl-7-(3,3-difluoro-pyrrolidin-1-yl)-2-ethyl-2H-[1,2,3]triazolo[4,5-d]pyrimidineHCID 178441792HCID 178441792, compound

Product 1

HCID 89586566(2S,3S)-1-[5-tert-Butyl-2-(1-cyclopropyl-1H-tetrazol-5-ylmethyl)-2H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl]-2-hydroxymethyl-pyrrolidin-3-ol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoro-pyrrolidin-1-yl)-2-ethyl-2H-[1,2,3]triazolo[4,5-d]pyrimidine (example 3, step b), the title compound was prepared from Trifluoro-acetic acid (2S,3S)-1-(5-tert-butyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)-2-(2,2,2-trifluoro-acetoxymethyl)-pyrrolidin-3-yl ester and 5-(chloromethyl)-1-cyclopropyl-1H-tetrazole. After completion of the substitution reaction methanol was added and the mixture was stirred for 1 h at room temperature and subsequently subjected to purification with preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. After evaporation of the product containing fractions the title compound was isolated as light-yellow solid. MS (m/e): 415.4 (MH+).

Workup

  1. additionwas added
  2. customsubsequently subjected to purification with preparative HPLC on reversed phase
  3. washeluting with a gradient
  4. customformed from acetonitrile, water and NEt3
  5. customAfter evaporation of the product
  6. additioncontaining fractions the title compound
  7. customwas isolated as light-yellow solid

Sources & evidence

ORD record
ord-969010256d7342378f2e4680afefcaaa
Source dataset
uspto-grants-2015_06
Patent number
US09067943B2

Reaction notes

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