Sodium cyanoborohydride → (R)-N-((5-(benzyloxymethyl)-4-tert-butoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-(methylthio)ethanamine

HRID 533222Notes

Reaction equation

HRID 533222 reaction equation
[CH3:1][C:2]1([CH3:12])[O:6][C@H:5]([C@@H:7]([NH2:11])[CH2:8][S:9][CH3:10])[CH2:4][O:3]1.C([BH3-])#N.[Na+].[CH2:17]([O:24][CH2:25][N:26]1[C:34]2[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[N:32][CH:31]=[N:30][C:29]=2[C:28]([CH:40]=O)=[CH:27]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:17]([O:24][CH2:25][N:26]1[C:34]2[C:33]([O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[N:32][CH:31]=[N:30][C:29]=2[C:28]([CH2:40][NH:11][C@H:7]([C@@H:5]2[CH2:4][O:3][C:2]([CH3:12])([CH3:1])[O:6]2)[CH2:8][S:9][CH3:10])=[CH:27]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

4

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 114277605-[(benzyloxy)methyl]-4-(tert-butoxy)-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehydeHCID 58287045HCID 58287045, compound

Product 1

HCID 67222111(R)-N-((5-(benzyloxymethyl)-4-tert-butoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-(methylthio)ethanamineYield 93%

Procedure

A mixture of the product from Example 27.4 (0.130 g, 0.68 mmol), sodium cyanoborohydride (0.071 g, 1.13 mmol) and 5-(benzyloxymethyl)-4-tert-butyloxy-5H-pyrrolo[3,2-d]pyrimidin-7-carbaldehyde (0.192 g, 0.57 mmol) were evaporated from methanol (3×). The residue was dissolved in methanol (10 ml) and acetic acid added (5 drops). The reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was evaporated on to silica gel and chromatographed (methanol-triethylamine-DCM, 3:1:96) giving an orange oil (0.272 g, 93%). 1H NMR indicated that the product contained some (co-polar) starting amine. 1H NMR (CDCl3) δ 8.47 (s, 1H), 7.38 (s, 1H), 7.34-7.22 (m, 5H), 5.73 (s, 2H), 4.47 (s, 2H), 4.34 (q, J=6.8 Hz, 1H), 4.10 (Abq, 2H), 4.03 (m, 1H), 3.82 (m, 1H), 2.87 (q, J=5.7 Hz; 1H), 2.72 (dd, J=13.2, 5.7 Hz, 1H), 2.60 (dd, J=13.2, 6.0 Hz, 1H), 2.05 (s, 3H), 1.69 (s, 9H), 1.39 (s, 3H), 1.34 (s, 3H).

Workup

  1. customwere evaporated from methanol (3×)
  2. dissolutionThe residue was dissolved in methanol (10 ml)
  3. additionacetic acid added (5 drops)
  4. customThe reaction mixture was evaporated on to silica gel
  5. customchromatographed (methanol-triethylamine-DCM, 3:1:96)

Sources & evidence

ORD record
ord-d085392c4038460791d6f8efb9182e8f
Source dataset
uspto-grants-2014_10
Patent number
US08853224B2

Reaction notes

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