Acetyl chloride → HCID 90409550, compound

HRID 589109Notes

Reaction equation

HRID 589109 reaction equation
F[C:2](F)(F)[C:3](O)=[O:4].FC(F)(F)C(O)=O.[NH2:15][CH2:16][C:17]1[C:22]([CH:23]2[N:28]3[C:29](=[O:42])[NH:30][C:31]4=[CH:32][CH:33]=[C:34]([C:35]5[C:36]([CH3:41])=[N:37][O:38][C:39]=5[CH3:40])[C:26](=[C:27]34)[O:25][CH2:24]2)=[CH:21][CH:20]=[CH:19][N:18]=1.C(N(CC)C(C)C)(C)C.C(Cl)(=O)C>C(Cl)Cl>[CH3:41][C:36]1[C:35]([C:34]2[C:26]3[O:25][CH2:24][CH:23]([C:22]4[C:17]([CH2:16][NH:15][C:3](=[O:4])[CH3:2])=[N:18][CH:19]=[CH:20][CH:21]=4)[N:28]4[C:29](=[O:42])[NH:30][C:31]([C:27]=34)=[CH:32][CH:33]=2)=[C:39]([CH3:40])[O:38][N:37]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 90409935HCID 90409935, compound

Product 1

HCID 90409550HCID 90409550, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-[2-(aminomethyl)pyridin-3-yl]-7-(3,5-dimethylisoxazol-4-yl)-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one bis(trifluoroacetate) (35.0 mg, 0.058 mmol) in methylene chloride (2.0 mL) was treated with N,N-diisopropylethylamine (50.3 μL, 0.289 mmol) and stirred. Once the starting material was completely dissolved, the reaction mixture was treated with acetyl chloride (49.3 μL, 0.069 mmol) (added as a 10% solution in dichloromethane) and stirred at room temperature for 1 h. The reaction mixture was quenched with methanol and the solvent was concentrated to give the crude product. Purification by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) gave the desired product (18 mg, 74%) as a racemic mixture. 1H NMR (500 MHz, DMSO-d6) δ 10.98 (br s, 1H), 8.50-8.47 (m, 1H), 8.44 (dd, J=5.2, 5.2 Hz, 1H), 7.26 (dd, J=7.9, 4.7 Hz, 1H), 7.23-7.16 (m, 1H), 6.88 (d, J=8.0 Hz, 1H), 6.78 (d, J=8.0 Hz, 1H), 5.68 (dd, J=3.1, 3.1 Hz, 1H), 4.71 (dd, J=15.1, 6.1 Hz, 1H), 4.55-4.47 (m, 2H), 4.44 (dd, J=11.6, 3.2 Hz, 1H), 2.28 (s, 3H), 2.12 (s, 3H), 1.88 (s, 3H); LCMS calculated for C22H22N5O4 (M+H)+: m/z=420.2. found: 420.1.

Workup

  1. dissolutionOnce the starting material was completely dissolved
  2. stirringstirred at room temperature for 1 h
  3. customThe reaction mixture was quenched with methanol
  4. concentrationthe solvent was concentrated
  5. customto give the crude product
  6. customPurification by preparative LCMS (XBridge C18 column
  7. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-ce6a3e064dd84737af8689d58dd0e257
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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