Sodium triacetoxyborohydride → HCID 67816383, compound

HRID 1054554Notes

Reaction equation

HRID 1054554 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.[CH3:25][C:26]1([CH3:52])[O:30][C@@H:29]2[C@@H:31]([CH2:47][NH:48][CH:49]([CH3:51])[CH3:50])[CH2:32][C@@H:33]([N:34]3[C:38]4[N:39]=[CH:40][N:41]=[C:42]([NH:43][CH:44]5[CH2:46][CH2:45]5)[C:37]=4[CH:36]=[CH:35]3)[C@@H:28]2[O:27]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][N:48]([CH2:47][C@@H:31]3[C@H:29]4[O:30][C:26]([CH3:52])([CH3:25])[O:27][C@H:28]4[C@H:33]([N:34]4[C:38]5[N:39]=[CH:40][N:41]=[C:42]([NH:43][CH:44]6[CH2:46][CH2:45]6)[C:37]=5[CH:36]=[CH:35]4)[CH2:32]3)[CH:49]([CH3:50])[CH3:51])=[N:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 67817502HCID 67817502, compoundHCID 86705754HCID 86705754, compound

Product 1

HCID 67816383HCID 67816383, compoundYield 74%

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 (0.285 g, 0.735 mmol) and 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.270 g, 0.700 mmol) were dissolved in DCE (17 ml) at r.t. under N2 and left for 15 mins. Sodium triacetoxyborohydride (0.208 g, 0.981 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 flash column chromatography using between 100% DCM to 15% MeOH:85% DCM as eluent to give the product as a white foam (0.392 g, 74%): MS (ESI+) for C38H55Cl2N7O3Si m/z 379.2 [M+H]2+, 756.4 [M+H]+; LC purity 100% (ret. time, 1.76 min); 1H NMR (500 MHz, CDCl3) δ 8.29 (s, 1H), 7.78 (s, 1H), 7.50 (s, 1H), 6.98 (d, J=3.63 Hz, 1H), 6.63 (br. s., 1H), 5.47 (br. s., 1H), 5.40 (s, 2H), 4.86-5.04 (m, 2H), 4.47 (br. s., 1H), 3.45-3.56 (m, 2H), 2.94-3.04 (m, 2H), 2.91 (t, J=7.72 Hz, 2H), 2.67 (br. s., 1H), 2.24-2.59 (m, 5H), 2.03 (br. s., 1H), 1.82-1.95 (m, 2H), 1.59 (br. s., 2H), 1.55 (s, 3H), 1.28 (s, 3H), 0.99 (br. s., 5H), 0.84-0.96 (m, 5H), 0.65-0.74 (m, 2H), −0.04 (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 flash column chromatography

Sources & evidence

ORD record
ord-ebbf7e64744a497d847196fc915341eb
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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