Sulfuric acid magnesium salt (1:1) → 7-[(3aS,4R,6R,6aR)-6-{[({3-[(5-tert-butyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)methyl]cyclobutyl}methyl)(propan-2-yl)amino]methyl}-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 511632Notes

Reaction equation

HRID 511632 reaction equation
[C:1]([C:5]1[CH:28]=[CH:27][C:8]2[N:9]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:10]([CH2:12][CH:13]3[CH2:16][CH:15]([CH:17]=O)[CH2:14]3)=[N:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:29][C:30]1([CH3:53])[O:34][C@@H:33]2[C@@H:35]([CH2:48][NH:49][CH:50]([CH3:52])[CH3:51])[CH2:36][C@@H:37]([N:38]3[C:42]4[N:43]=[CH:44][N:45]=[C:46]([NH2:47])[C:41]=4[CH:40]=[CH:39]3)[C@@H:32]2[O:31]1.S([O-])([O-])(=O)=O.[Mg+2].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([C:5]1[CH:28]=[CH:27][C:8]2[N:9]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:24])([CH3:26])[CH3:25])[C:10]([CH2:12][CH:13]3[CH2:16][CH:15]([CH2:17][N:49]([CH2:48][C@@H:35]4[C@H:33]5[O:34][C:30]([CH3:53])([CH3:29])[O:31][C@H:32]5[C@H:37]([N:38]5[C:42]6[N:43]=[CH:44][N:45]=[C:46]([NH2:47])[C:41]=6[CH:40]=[CH:39]5)[CH2:36]4)[CH:50]([CH3:52])[CH3:51])[CH2:14]3)=[N:11][C:7]=2[CH:6]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 5049666Sodium triacetoxyborohydrideHCID 677763337-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineHCID 866661243-[(5-tert-butyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)methyl]cyclobutane-1-carbaldehyde

Product 1

HCID 677748577-[(3aS,4R,6R,6aR)-6-{[({3-[(5-tert-butyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)methyl]cyclobutyl}methyl)(propan-2-yl)amino]methyl}-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 11.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

3-[(5-Tert-butyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)methyl]cyclobutane-1-carbaldehyde (282.3 mg, 0.7 mmol), 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (243.41 mg, 0.7 mmol) and magnesium sulfate (127.22 mg, 1.06 mmol) were stirred in 1,2-dichloroethane (10 ml) for 15 mins. Sodium triacetoxyborohydride (179.21 mg, 0.85 mmol) was added, and the reaction stirred overnight. The reaction was quenched by the addition of sat. Na2CO3 (10 ml), and the solution was extracted with DCM (3×10 ml). The combined organics were dried (MgSO4) and concentrated. The crude material was purified by mass directed prep-HPLC (acidic method). After combining the fractions, a small amount of 7M NH3 in MeOH was added to basify the solution. After concentration, the residue was partitioned between water (5 ml) and DCM (5 ml), and the layers separated. The aqueous layer was extracted with DCM (2×3 ml) and the combined organics were dried (MgSO4) and concentrated to afford the title compound (58.7 mg, 11%) as a colourless gum: MS (ESI) for C41H63N7O3Si m/z 730.2 [M+H]+; LC purity 95% (UV), 100% (ELS), (ret. time, 1.65 min); 1H NMR (500 MHz, CHLOROFORM-d) δH 8.30 (s, 1H), 7.75 (s, 1H), 7.32 (s, 2H), 7.04 (d, J=3.6 Hz, 1H), 6.37 (d, J=3.6 Hz, 1H), 5.40-5.50 (m, 2H), 5.24 (br. s., 2H), 4.89-5.04 (m, 2H), 4.45 (d, J=5.2 Hz, 1H), 3.50 (s, 3H), 2.11-3.09 (m, 13H), 2.01 (s, 6H), 1.34-1.49 (m, 6H), 1.29 (s, 3H), 0.85-1.02 (m, 8H), −0.11-0.05 (m, 9H).

Workup

  1. customThe reaction was quenched by the addition of sat. Na2CO3 (10 ml)
  2. extractionthe solution was extracted with DCM (3×10 ml)
  3. dry with materialThe combined organics were dried (MgSO4)
  4. concentrationconcentrated
  5. customThe crude material was purified by mass
  6. additiona small amount of 7M NH3 in MeOH was added
  7. concentrationAfter concentration
  8. customthe residue was partitioned between water (5 ml) and DCM (5 ml)
  9. customthe layers separated
  10. extractionThe aqueous layer was extracted with DCM (2×3 ml)
  11. dry with materialthe combined organics were dried (MgSO4)
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-21b785a20d944542b57aa61b385cbed6
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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