Aluminium lithium hydride → 2-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-1,2,3-triazolo(4,5-d)pyrimidin-3-yl)tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl)oxy)ethanol

HRID 2172668Notes

Reaction equation

HRID 2172668 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:9]=[C:10]([C@@H:15]2[CH2:17][C@H:16]2[NH:18][C:19]2[C:20]3[N:31]=[N:30][N:29]([C@H:32]4[C@@H:36]5[O:37][C:38]([CH3:41])([CH3:40])[O:39][C@@H:35]5[C@@H:34]([O:42][CH2:43][C:44](O)=[O:45])[CH2:33]4)[C:21]=3[N:22]=[C:23]([S:25][CH2:26][CH2:27][CH3:28])[N:24]=2)[CH:11]=[CH:12][C:13]=1[F:14]>C1COCC1>[F:7][C:8]1[CH:9]=[C:10]([C@@H:15]2[CH2:17][C@H:16]2[NH:18][C:19]2[C:20]3[N:31]=[N:30][N:29]([C@H:32]4[C@@H:36]5[O:37][C:38]([CH3:40])([CH3:41])[O:39][C@@H:35]5[C@@H:34]([O:42][CH2:43][CH2:44][OH:45])[CH2:33]4)[C:21]=3[N:22]=[C:23]([S:25][CH2:26][CH2:27][CH3:28])[N:24]=2)[CH:11]=[CH:12][C:13]=1[F:14]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 665758732-((3aR,4S,6R,6aS)-6-(7-((1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yloxy)acetic acid

Product 1

HCID 672892902-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3H-1,2,3-triazolo(4,5-d)pyrimidin-3-yl)tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl)oxy)ethanolYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

LiAlH4 (0.151 g) was added to THF (35 mL) slowly at −10° C. To this mixture was added a solution of compound 11a (1.5 g) in THF (15 mL) slowly over 30 min at 0 to −10° C. The reaction mixture was stirred at 0 to −10° C. for 2 hrs. The reaction was monitored by TLC. When the reaction was complete, it was quenched by addition of aqueous saturated ammonium chloride (10 mL), followed by addition of ethyl acetate (20 mL). The phases were separated and the organic phase was concentrated. The residue was purified by column chromatography (eluting with 40% ethyl acetate in hexane). The fractions containing the product were concentrated under reduced pressure to provide compound 12 as an oily mass (0.7 g, 70-75% yield).

Workup

  1. customit was quenched by addition of aqueous saturated ammonium chloride (10 mL)
  2. additionfollowed by addition of ethyl acetate (20 mL)
  3. customThe phases were separated
  4. concentrationthe organic phase was concentrated
  5. customThe residue was purified by column chromatography (eluting with 40% ethyl acetate in hexane)
  6. additionThe fractions containing the product
  7. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-b9d08ab5fb034c3a9c0776aa7fc87a10
Source dataset
uspto-grants-2015_06
Patent number
US09056838B2

Reaction notes

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