Lithium borohydride → (2S,3R)-3-((5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)butane-1,2,4-triol

HRID 533212Notes

Reaction equation

HRID 533212 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[C:18]2[C:17]([O:19][CH3:20])=[N:16][CH:15]=[N:14][C:13]=2[C:12]([CH2:21][NH:22][C@H:23]([C@H:29]([OH:35])[C:30](OCC)=[O:31])[C:24](OCC)=[O:25])=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Li+]>C(OCC)C.CO>[CH2:1]([O:8][CH2:9][N:10]1[C:18]2[C:17]([O:19][CH3:20])=[N:16][CH:15]=[N:14][C:13]=2[C:12]([CH2:21][NH:22][C@H:23]([CH2:24][OH:25])[C@H:29]([OH:35])[CH2:30][OH:31])=[CH:11]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 4148881Lithium borohydrideHCID 25223389(2R,3S)-diethyl 2-((5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-3-hydroxysuccinate

Product 1

HCID 25223390(2S,3R)-3-((5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)butane-1,2,4-triolYield 66.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 3283Diethyl EtherSolvent

Procedure

To a stirred solution of the product from Example 17.1 (1.718 g, 3.53 mmol) in diethyl ether (30 ml) was added methanol (1.43 ml, 35.3 mmol) and then lithium borohydride (8.83 ml, 17.7 mmol, 2.0M in THF). After 1 h methanol (1.43 ml, 35.3 mmol) was added to the reaction mixture and stirring continued. After 1 h further the reaction mixture was diluted with methanol and then concentrated. The residue was dissolved in methanol (20 ml), diluted with hydrochloric acid (20 ml, 1M) and concentrated. The residue was chromatographed on silica gel (methanol [7N ammonia]-DCM, 15:85) giving a white solid (0.940 g, 66%). 1H NMR (CD3OD) δ 8.43 (s, 1H), 7.69 (s, 1H), 7.28-7.15 (m, 5H), 5.77 (s, 2H), 4.52 (s, 2H), 4.12 (ABq, 2H), 4.11 (s, 31-1), 3.80 (dd, J=11.7, 5.3 Hz, 1H), 3.80-3.60 (m, 3H), 3.59 (dd, J=11.0, 4.9 Hz, 1H), 2.90 (q, J=4.9 Hz, 1H). 13C NMR (CD3OD) δ 158.4, 151.4, 151.0, 139.1, 135.0, 129.7, 129.2, 129.1, 117.5, 115.3, 79.0, 72.5, 72.0, 65.6, 62.0, 61.6, 54.8, 42.1.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in methanol (20 ml)
  3. additiondiluted with hydrochloric acid (20 ml, 1M)
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel (methanol [7N ammonia]-DCM, 15:85)

Sources & evidence

ORD record
ord-fb802b51768a4fd49121eec2d69a2275
Source dataset
uspto-grants-2014_10
Patent number
US08853224B2

Reaction notes

Loading…