(4-Chlorophenyl)acetic acid → 2-(4-chlorophenyl)-N-[2-[[(1R)-2,3-dihydro-1H-inden-1-yl]amino]-4H-3,1-benzoxazin-5-yl]acetamide

HRID 1666106Notes

Reaction equation

HRID 1666106 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[C@H:43]1([NH:52][C:53]2[O:54][CH2:55][C:56]3[C:62]([NH2:63])=[CH:61][CH:60]=[CH:59][C:57]=3[N:58]=2)[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH2:45][CH2:44]1>ClCCl.CN(C)C=O.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:63][C:62]2[C:56]3[CH2:55][O:54][C:53]([NH:52][C@H:43]4[C:51]5[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=5)[CH2:45][CH2:44]4)=[N:58][C:57]=3[CH:59]=[CH:60][CH:61]=2)=[O:11])=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 15880(4-Chlorophenyl)acetic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 178507384HCID 178507384, compound

Product 1

HCID 1785202752-(4-chlorophenyl)-N-[2-[[(1R)-2,3-dihydro-1H-inden-1-yl]amino]-4H-3,1-benzoxazin-5-yl]acetamideYield 41%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-Chlorophenylacetic acid (122 mg, 0.65 mmol), N,N-diisopropyl ethyl amine (245 mg, 1.9 mmol) and 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (254 mg, 0.79 mmol) were dissolved in dichloromethane (5 mL) and dimethylformamide (1 mL). The reaction mixture was stirred at room temperature for 30 minutes. (R)—N2-Indan-1-yl-4H-benzo[d][1,3]oxazine-2,5-diamine (example 2) (150 mg, 0.54 mmol) was added and stirring was continued overnight. The reaction mixture was diluted with water and extracted twice with dichloromethane. The combined organic phases were dried over sodium sulfate and evaporated. The crude product was recrystallized from isopropanol and diisopropylether. The title compound (95 mg, 41%) was obtained as a white solid; MS: m/e=430.5 (M−H+).

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. extractionextracted twice with dichloromethane
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. customevaporated
  6. customThe crude product was recrystallized from isopropanol and diisopropylether

Sources & evidence

ORD record
ord-d13056a543ab4895bbe82959c0bc5c62
Source dataset
uspto-grants-2011_10
Patent number
US08044047B2

Reaction notes

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