Acetic Acid → HCID 66547140, compound

HRID 403261Notes

Reaction equation

HRID 403261 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@:8]2([CH3:17])[C@@H:14]([F:15])[CH2:13][O:12][CH2:11][C:10]([NH2:16])=[N:9]2)[CH:7]=1.[Cl:19][C:20]1[CH:21]=[N:22][C:23]2[C:24](=O)[CH2:25][CH2:26][C:27]=2[CH:28]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCCl>[Cl:19][C:20]1[CH:28]=[C:27]2[CH2:26][CH2:25][CH:24]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@:8]4([CH3:17])[C@@H:14]([F:15])[CH2:13][O:12][CH2:11][C:10]([NH2:16])=[N:9]4)[CH:7]=3)[C:23]2=[N:22][CH:21]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 58082858HCID 58082858, compoundHCID 58562930HCID 58562930, compound

Product 1

HCID 66547140HCID 66547140, compoundYield 34.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of (5R,6R)-5-(5-amino-2-fluoro-phenyl)-6-fluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-ylamine (intermediate A10B) (20 mg, 78.4 μmol) in 1,2-dichloroethane (200 μl) was added at 23° C. under inert atmosphere 3-chloro-5,6-dihydro-[1]pyrindin-7-one (14.4 mg, 86.2 μmol) and acetic acid (9.41 mg, 8.97 μl, 157 μmol) and the solution was stirred at 23° C. for 30 min. Then sodium triacetoxyborohydride (24.9 mg, 118 μmol) was added and the mixture was stirred at 23° C. for 4 h. After addition of 1 M HCl (1 ml) and stirring for 10 min, the aqueous layer was washed once with dichloromethane, then treated with sat. Na2CO3-sol. to achieve pH 14 and extracted twice with ethyl acetate. The combined organic layers were dried over Na2SO4 and evaporated to give a crude product, which was purified by basic preparative HPLC to give (5R,6R)-5-(5-(3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ylamino)-2-fluorophenyl)-6-fluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine (11 mg, 27.0 μmol, 34.5% yield) as a colorless oil. MS (ISP): m/z=407.3.3 [(M+H)+] and 409.3 [(M+2+H)+].

Workup

  1. stirringthe mixture was stirred at 23° C. for 4 h
  2. stirringstirring for 10 min
  3. washthe aqueous layer was washed once with dichloromethane
  4. additiontreated with sat. Na2CO3-sol
  5. extractionextracted twice with ethyl acetate
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. customevaporated
  8. customto give a crude product, which
  9. customwas purified by basic preparative HPLC

Sources & evidence

ORD record
ord-bb503a4768564a9a9f0a8a264ff8a28c
Source dataset
uspto-grants-2014_06
Patent number
US08748418B2

Reaction notes

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