Sulfuric acid magnesium salt (1:1) → (R)-N-benzyl-1-(5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)methanamine

HRID 533186Notes

Reaction equation

HRID 533186 reaction equation
[CH2:1]([NH:8][CH2:9][C@@H:10]1[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:17]([O:24][CH2:25][N:26]1[C:34]2[C:33]([O:35][CH3:36])=[N:32][CH:31]=[N:30][C:29]=2[C:28]([CH:37]=O)=[CH:27]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[O-]S([O-])(=O)=O.[Mg+2]>ClCCCl.C(Cl)Cl>[CH2:1]([N:8]([CH2:9][C@@H:10]1[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11]1)[CH2:37][C:28]1[C:29]2[N:30]=[CH:31][N:32]=[C:33]([O:35][CH3:36])[C:34]=2[N:26]([CH2:25][O:24][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:27]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 5049666Sodium triacetoxyborohydrideHCID 25223591(R)-N-benzyl-1-(2,2-dimethyl-1,3-dioxolan-4-yl)methanamineHCID 577250835-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde

Product 1

HCID 58287034(R)-N-benzyl-1-(5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)methanamineYield 74.7%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)—N-benzyl-1-(2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (0.372 g, 1.682 mmol) and 5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde (0.5 g, 1.682 mmol) in 1,2-dichloroethane (30 ml) was added sodium triacetoxyborohydride (0.463 g, 2.186 mmol) and anhydrous MgSO4 (1 g). The mixture was stirred for 6 h. Tlc (EtOAc-hexanes, 8:2) showed the reaction essentially over. After diluting with CH2Cl2 the mixture was washed with aqueous sat. NaHCO3, brine, dried and the solvent evaporated. The residue was chromatographed (EtOAc-hex, 1:1, uv and molybdate) to give (R)—N-benzyl-1-(5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)methanamine (0.631 g, 1.255 mmol, 74.7% yield) as a colourless gum. [α]D21 −21.9 (c, 0.905, MeOH). 1H NMR (CDCl3, 300 MHz), 5 ppm, 8.55 (s, 1H), 7.41 (s, 1H), 7.37-7.18 (m, 10H), 5.73 (s, 2H), 4.46 (s, 2H), 4.38-4.29 (m, 1H), 4.10, (s, 3H), 4.05-3.98 (m, 2H), 3.79 (d, 1H, J 13.9 Hz), 3.63 (d, 1H, J 13.9 Hz), 3.53, (t, 1H, J 7.9 Hz), 2.73 (dd, 1H, J 13.3, 5.9 Hz), 2.64 (dd, 1H, J 13.3, 5.9 Hz), 1.32 (s, 6H). 13C NMR (CDCl3, 75.5 MHz), δ ppm, 156.2 (C), 150.7 (C), 150.0 (CH), 139.6 (C), 136.9 (C), 132.2 (CH), 128.8 (CH), 128.4 (CH), 128.2 (CH), 128.0 (CH), 127.7 (CH), 126.9 (CH), 115.7 (C), 114.7 (C), 109.0 (C), 77.0 (CH2), 74.7 (CH2), 70.1 (CH2), 68.4 (CH2), 59.2 (CH2), 56.2 (CH2) 53.5 (CH3), 47.8 (CH2), 26.8 (CH3), 25.6 (CH3). +ESMS Found 503.2643 (M+H)+ C29H35N4O4 requires 503.2658.

Workup

  1. customthe reaction essentially over
  2. washwas washed with aqueous sat. NaHCO3, brine
  3. customdried
  4. customthe solvent evaporated
  5. customThe residue was chromatographed (EtOAc-hex, 1:1, uv and molybdate)

Sources & evidence

ORD record
ord-3149c020998041148d3fd9b311570fa8
Source dataset
uspto-grants-2014_10
Patent number
US08853224B2

Reaction notes

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