Methanol → 4-amino-1-((2R,3S,4S,5R)-5-(difluoromethyl)-3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-one

HRID 2205188Notes

Reaction equation

HRID 2205188 reaction equation
B(Cl)(Cl)Cl.[NH2:5][C:6]1[CH:11]=[CH:10][N:9]([C@H:12]2[C@@H:16]([OH:17])[C@H:15]([O:18]CC3C=CC=CC=3)[C@:14]([CH2:29][O:30]CC3C=CC=CC=3)([CH:26]([F:28])[F:27])[O:13]2)[C:8](=[O:38])[N:7]=1.N1C=CC=CC=1.CO>ClCCl>[NH2:5][C:6]1[CH:11]=[CH:10][N:9]([C@H:12]2[C@@H:16]([OH:17])[C@H:15]([OH:18])[C@@:14]([CH:26]([F:28])[F:27])([CH2:29][OH:30])[O:13]2)[C:8](=[O:38])[N:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 1049PyridineHCID 25135Boron TrichlorideHCID 1182943934-amino-1-((2R,3S,4S,5R)-4-(benzyloxy)-5-(benzyloxymethyl)-5-(difluoromethyl)-3-hydroxy-tetrahydrofuran-2-yl)pyrimidin-2(1H)-one

Product 1

HCID 1182941754-amino-1-((2R,3S,4S,5R)-5-(difluoromethyl)-3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-oneYield 47.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

BCl3 (3.7 mL, 3.7 mmol) was added to a solution of compound 37 (0.175 g, 0.37 mmol) in dichloromethane (10 mL) cooled to −78° C. The reaction was stirred at −78° C. for 3 h, then warmed to 25° C. and stirred for a further 12 h. The reaction mixture was cooled to 0° C. and then pyridine was added into the mixture, followed by methanol. The reaction mixture was evaporated to dryness under reduced pressure. Purification by prep-HPLC afforded the product 38 (0.052 g, 41%) as a white solid. LC-MS (M+H)+=294.1

Workup

  1. temperaturewarmed to 25° C.
  2. stirringstirred for a further 12 h
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. customThe reaction mixture was evaporated to dryness under reduced pressure
  5. customPurification

Sources & evidence

ORD record
ord-ab6c6fc879d04e28bfe29fc09607fd24
Source dataset
uspto-grants-2016_06
Patent number
US09370569B2

Reaction notes

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