Water → (S)-3-chloro-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazine]-2',7-diamine

HRID 931644Notes

Reaction equation

HRID 931644 reaction equation
[N:1]([C:4]1[CH:5]=[C:6]2[C@@:17]3([CH2:22][CH2:21][O:20][C:19]([NH2:23])=[N:18]3)[C:16]3[CH:15]=[C:14]([Cl:24])[N:13]=[C:12]([F:25])[C:11]=3[O:10][C:7]2=[CH:8][CH:9]=1)=[N+]=[N-].[BH4-].[Na+].O>CO>[Cl:24][C:14]1[N:13]=[C:12]([F:25])[C:11]2[O:10][C:7]3[C:6]([C@@:17]4([CH2:22][CH2:21][O:20][C:19]([NH2:23])=[N:18]4)[C:16]=2[CH:15]=1)=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=3

Participants

5

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydrideHCID 117600848(S)-7-azido-3-chloro-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazin]-2'-amine

Product 1

HCID 90158687(S)-3-chloro-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazine]-2',7-diamineYield 44.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-7-azido-3-chloro-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-2′-amine (0.86 g, 2.384 mmol) in MeOH (15 mL) in a water bath was added sodium borohydride (0.420 ml, 11.92 mmol) in one portion. The resulting mixture was kept in the water bath and stirred for 10 min. The reaction went to completion and was carefully quenched with water, diluted with DCM and washed with 9:1 NH4OH/sat NH4Cl (10 mL). The combined organics were dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-5% MeOH/DCM to afford a pale yellow solid as (S)-3-chloro-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazine]-2′,7-diamine (0.354 g, 1.058 mmol, 44.4% yield).

Workup

  1. customwas carefully quenched with water
  2. additiondiluted with DCM
  3. washwashed with 9:1 NH4OH/
  4. dry with materialThe combined organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed on silica gel using 0-5% MeOH/DCM

Sources & evidence

ORD record
ord-456be2bda9ce498d85127a273810ae4c
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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