Hydrochloric Acid → (4aR,7aR)-6-(5-Fluoropyrimidin-2-yl)-7a-(2-thienyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-amine hydrochloride

HRID 338167Notes

Reaction equation

HRID 338167 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:16][C@@H:15]3[C@@:10]([C:18]4[S:19][CH:20]=[CH:21][CH:22]=4)([N:11]=[C:12]([NH2:17])[S:13][CH2:14]3)[CH2:9]2)=[N:6][CH:7]=1.COC(C)(C)C.[ClH:29]>C(OCC)(=O)C>[ClH:29].[F:1][C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:16][C@@H:15]3[C@@:10]([C:18]4[S:19][CH:20]=[CH:21][CH:22]=4)([N:11]=[C:12]([NH2:17])[S:13][CH2:14]3)[CH2:9]2)=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 15413tert-Butyl methyl etherHCID 78318766(4aR,7aR)-6-(5-Fluoropyrimidin-2-yl)-7a-(2-thienyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-amine

Product 1

HCID 78318765(4aR,7aR)-6-(5-Fluoropyrimidin-2-yl)-7a-(2-thienyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-amine hydrochlorideYield 97.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4aR,7aR)-6-(5-fluoropyrimidin-2-yl)-7a-(2-thienyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-amine (3.8 g, 11.33 mmol) in a solution of methyl-t-butyl ether (50 mL) and ethyl acetate (10 mL) is treated with hydrogen chloride (1 M in diethyl ether) (13.6 mL, 13.6 mmol). The mixture is stirred for 10 minutes, concentrated and the product is dried under vacuum to give the title compound (4.1 g, 97%). ES/MS (m/e): 336 (M+H). Chiral analysis: (Column: Chiralpak AS (5u), C18 4.6×100 mm; eluent: 25% methanol with 0.2% dimethylethylamine) in CO2; flow 2.5 mL/min at UV 220 nm) to confirm the title compound, (>99% ee, Rt=1.44 min)

Workup

  1. concentrationconcentrated
  2. customthe product is dried under vacuum

Sources & evidence

ORD record
ord-3ac09b33d25b4949bf5d21d35bdc88ca
Source dataset
uspto-grants-2014_11
Patent number
US08889856B2

Reaction notes

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