Sodium triacetoxyborohydride → HCID 67818137, compound

HRID 1054552Notes

Reaction equation

HRID 1054552 reaction equation
[Cl:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]2[N:6]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:7]([CH2:9][CH2:10][CH2:11][CH:12]=O)=[N:8][C:4]=2[CH:3]=1.[NH2:25][CH2:26][C@@H:27]1[C@H:31]2[O:32][C:33]([CH3:36])([CH3:35])[O:34][C@H:30]2[C@H:29]([N:37]2[C:41]3[N:42]=[CH:43][N:44]=[C:45]([NH:46][CH:47]4[CH2:49][CH2:48]4)[C:40]=3[CH:39]=[CH:38]2)[CH2:28]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]2[N:6]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:19])([CH3:21])[CH3:20])[C:7]([CH2:9][CH2:10][CH2:11][CH2:12][NH:25][CH2:26][C@@H:27]3[C@H:31]4[O:32][C:33]([CH3:35])([CH3:36])[O:34][C@H:30]4[C@H:29]([N:37]4[C:41]5[N:42]=[CH:43][N:44]=[C:45]([NH:46][CH:47]6[CH2:49][CH2:48]6)[C:40]=5[CH:39]=[CH:38]4)[CH2:28]3)=[N:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 67816524HCID 67816524, compoundHCID 86705754HCID 86705754, compound

Product 1

HCID 67818137HCID 67818137, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

4-(5,6-Dichloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl)butanal (0.310 g, 0.801 mmol) and 7-[(3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.262 g, 0.763 mmol) were dissolved in DCE (17 ml) at r.t. under N2 and left for 15 mins. Sodium triacetoxyborohydride (0.226 g, 1.07 mmol) was added and the reaction left overnight. The reaction was quenched by the addition of sat. Na2CO3 solution (20 ml) and DCM (20 ml). The organic layer was separated and the aqueous layer was extracted with DCM (3×20 ml). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give the crude product. The product was purified by silica flash column chromatography using between 100% DCM to 10% MeOH:90% DCM as eluent to give the product as a white foam (0.222 g, 41%): MS (ESI+) for C35H49Cl2N7O3Si m/z 714.4 [M+H]+; LC purity 99% (ret. time, 1.73 min); 1H NMR (500 MHz, CDCl3) δ 8.28 (s, 1H), 7.80 (s, 1H), 7.51 (s, 1H), 7.00 (d, J=3.63 Hz, 1H), 6.64 (br. s., 1H), 5.62 (br. s., 1H), 5.42 (s, 2H), 4.91-5.03 (m, 2H), 4.55 (t, J=6.23 Hz, 1H), 3.45-3.59 (m, 2H), 2.90-3.02 (m, 3H), 2.82-2.89 (m, 1H), 2.69-2.81 (m, 3H), 2.45 (dt, J=12.61, 6.46 Hz, 1H), 2.35 (tt, J=12.41, 6.27 Hz, 1H), 2.16 (q, J=11.98 Hz, 1H), 1.97 (dt, J=15.41, 7.66 Hz, 2H), 1.69 (quin, J=7.37 Hz, 2H), 1.57 (s, 3H), 1.30 (s, 3H), 0.85-0.99 (m, 4H), 0.64-0.76 (m, 2H), −0.03 (s, 9H).

Workup

  1. waitthe reaction left overnight
  2. customThe reaction was quenched by the addition of sat. Na2CO3 solution (20 ml) and DCM (20 ml)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with DCM (3×20 ml)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customThe product was purified by silica flash column chromatography

Sources & evidence

ORD record
ord-7b76be57c89345b893e6dc4143bc1020
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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