Ethyl Acetate → 2-{(3S)-7-Chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetamide

HRID 1054186Notes

Reaction equation

HRID 1054186 reaction equation
C1C[N:4]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Cl:34][C:35]1[CH:61]=[CH:60][C:38]2[N:39]([C:47]([C:49]3[CH:50]=[CH:51][C:52]4[O:57][CH2:56][C:55](=[O:58])[NH:54][C:53]=4[CH:59]=3)=[O:48])[C@@H:40]([CH2:43][C:44]([OH:46])=O)[CH2:41][O:42][C:37]=2[CH:36]=1.[NH4+].[Cl-].CCOC(C)=O>C(Cl)Cl>[Cl:34][C:35]1[CH:61]=[CH:60][C:38]2[N:39]([C:47]([C:49]3[CH:50]=[CH:51][C:52]4[O:57][CH2:56][C:55](=[O:58])[NH:54][C:53]=4[CH:59]=3)=[O:48])[C@@H:40]([CH2:43][C:44]([NH2:4])=[O:46])[CH2:41][O:42][C:37]=2[CH:36]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 2724699PyBOPHCID 1185997562-[(3S)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetic acid2×

Product 1

HCID 1185996152-{(3S)-7-Chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetamideYield 52.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

PyBOP (127 mg, 0.24 mmol) and TEA (0.141 mL, 1.02 mmol) was added to a solution of {(3S)-7-chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetic acid (Intermediate 22a, 82 mg, 0.20 mmol) in DCM (2 mL). Thereafter, NH4Cl (43.6 mg, 0.81 mmol) was added and the mixture was stirred at rt for 1.5 h. EtOAc (30 mL) was added and the mixture was washed with sat. aq. Na2CO3 (30 mL), HCl (0.5M, 20 mL) and brine (20 mL). The product was purified by preparative HPLC (Phenomenex Luna Hilic column (5 μm 250×30 ID mm) using a gradient of 10 to 45% MeOH/DEA 100/0.5 in CO2, 120 bar, over 6 min at 40 OC) to give the title compound (42.0 mg, 51.3%).

Workup

  1. washthe mixture was washed with sat. aq. Na2CO3 (30 mL), HCl (0.5M, 20 mL) and brine (20 mL)
  2. customThe product was purified by preparative HPLC (Phenomenex Luna Hilic column (5 μm 250×30 ID mm)

Sources & evidence

ORD record
ord-d5c4373958854305951d9d7de9d84459
Source dataset
uspto-grants-2016_07
Patent number
US09394291B2

Reaction notes

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