Methylamine → HCID 178485279, compound

HRID 1672441Notes

Reaction equation

HRID 1672441 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[N:18]=[CH:17][C:16]3[C:11](=[CH:12][C:13]([C:19]([OH:21])=O)=[CH:14][CH:15]=3)[N:10]=2)[CH2:4][CH2:3]1.C[CH2:23][N:24]=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CN>CN(C=O)C>[OH:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([NH:8][C:9]2[N:18]=[CH:17][C:16]3[C:11](=[CH:12][C:13]([C:19]([NH:24][CH3:23])=[O:21])=[CH:14][CH:15]=3)[N:10]=2)[CH2:6][CH2:7]1

Participants

7

Reactant 5

HCID 6329MethylamineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178524134HCID 178524134, compound

Product 1

HCID 178485279HCID 178485279, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[(trans-4-hydroxycyclohexyl)amino]quinazoline-7-carboxylic acid (116 mg, 0.404 mmol) in DMF (3 mL) was added EDCl (93 mg, 0.484 mmol), HOBt (60 mg, 0.444 mmol), NMM (0.111 mL, 1.01 mmol) followed by the methylamine solution (2 M in THF, 0.303 mL, 0.606 mmol) and the mixture stirred at ambient temperature for 16 hours. The solvents were removed in vacuo and the residue azeotroped with MeOH (10 mL). The resulting yellow gum was purified directly by Biotage 25M; loaded in 2% MeOH/CH2Cl2, and eluted with 2-7% MeOH/CH2Cl2 over 520 mL. Product not fully eluted so continued over another 300 mL to 10% MeOH/CH2Cl2 to give a solid that was then triturated with EtOAc, filtered and dried in vacuo to yield the title compound as a yellow solid, 78 mg, 65%. 1H NMR (400 MHz, DMSO-D6) δ ppm 9.11 (1H, s) 8.68 (1H, d, J=3.54 Hz) 7.90 (1H, s) 7.81 (1H, d, J=8.34 Hz) 7.57 (1H, d, J=8.34 Hz) 7.39 (1H, d, J=6.57 Hz) 4.56 (1H, d, J=4.29 Hz) 3.79 (1H, s) 3.36-3.50 (1H, m) 2.79 (3H, d, J=4.55 Hz) 1.80-2.03 (4H, m) 1.17-1.43 (4H, m); MS (API+) for C16H20N4O2 m/z 301.2 (M+H)+.

Workup

  1. customThe solvents were removed in vacuo
  2. customthe residue azeotroped with MeOH (10 mL)
  3. customThe resulting yellow gum was purified directly by Biotage 25M
  4. washeluted with 2-7% MeOH/CH2Cl2 over 520 mL
  5. washProduct not fully eluted
  6. customto give a solid
  7. customthat was then triturated with EtOAc
  8. filtrationfiltered
  9. customdried in vacuo

Sources & evidence

ORD record
ord-176249f2485644d380bc9266c66f851b
Source dataset
uspto-grants-2011_08
Patent number
US07998978B2

Reaction notes

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