Acetanthranil → 2-methyl-3-[2-((R)-3-piperidin-1-yl-pyrrolidin-1-yl)-benzothiazol-6-yl]-3H-quinazolin-4-one

HRID 2041003Notes

Reaction equation

HRID 2041003 reaction equation
[N:1]1([C@@H:7]2[CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]4[CH:20]=[C:19]([NH2:21])[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:22][C:23]1[O:24][C:25](=O)[C:26]2[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=2[N:28]=1>C(O)(=O)C>[CH3:22][C:23]1[N:21]([C:19]2[CH:18]=[CH:17][C:15]3[N:16]=[C:12]([N:9]4[CH2:10][CH2:11][C@@H:7]([N:1]5[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]5)[CH2:8]4)[S:13][C:14]=3[CH:20]=2)[C:25](=[O:24])[C:26]2[C:27](=[CH:29][CH:30]=[CH:31][CH:32]=2)[N:28]=1

Participants

4

Reactant 2

HCID 68236AcetanthranilHCID 66905493(R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-amine

Product 1

HCID 441254462-methyl-3-[2-((R)-3-piperidin-1-yl-pyrrolidin-1-yl)-benzothiazol-6-yl]-3H-quinazolin-4-one

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-amine (Example 89A, 27 mg, 0.089 mmol) and 2-methyl-4H-benzo[d][1,3]oxazin-4-one (Example 89B, 14.39 mg, 0.089 mmol) in acetic acid (1 mL) was heated in a microwave reactor to 160° C. for 20 minutes. The mixture was concentrated under reduced pressure and chromatographed on silica gel column eluting with 2% (9:1 methanol:concentrated NH4OH) in dichloromethane to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.45-1.53 (m, 2H), 1.58-1.70 (m, 4H), 1.98-2.12 (m, 1H), 2.26-2.30 (m, J=1.36 Hz, 3H), 2.29-2.37 (m, 1H), 2.42-2.58 (m, 4H), 2.94-3.10 (m, J=8.48 Hz, 1H), 3.39-3.51 (m, 1H), 3.52-3.64 (m, 1H), 3.71-3.94 (m, 2H), 7.14 (dd, 1H), 7.43-7.51 (m, 2H), 7.66-7.72 (m, 2H), 7.74-7.81 (m, 1H), 8.24-8.31 (m, 1H); MS (DCI/NH3) m/z 387 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customchromatographed on silica gel column
  3. washeluting with 2% (9:1 methanol:concentrated NH4OH) in dichloromethane

Sources & evidence

ORD record
ord-9d52046ffb3b468b9f3f8d59c80b4871
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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