4-Hydroxycyclohexanone → HCID 59239193, compound

HRID 1698049Notes

Reaction equation

HRID 1698049 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[C:16]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].[OH:30][CH:31]1[CH2:36][CH2:35]C(=O)[CH2:33][CH2:32]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.CN(C=O)C>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]=[C:15]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[C:16]3[CH2:22][CH2:21][N:20]([CH:23]4[CH2:35][CH2:36][CH:31]([OH:30])[CH2:32][CH2:33]4)[CH2:19][C:17]=3[N:18]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2].[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]=[C:15]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[C:16]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][C:17]=3[N:18]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 5437064-HydroxycyclohexanoneHCID 5049666Sodium triacetoxyborohydrideHCID 46913263HCID 46913263, compound

Product 2

HCID 46913263HCID 46913263, compoundHCID 59239193HCID 59239193, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 20184825Dce dmfSolvent

Conditions

Temperature
75 °C

Procedure

and 1-ethyl-3-(4-(7-methyl-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (yf): A mixture of compound 1 (200 mg, 0.52 mmol) and 4-hydroxycyclohexanone (97.9 mg, 0.85 mmol) in a mixed solvent of DCE/DMF (3:5, 10 mL) was stirred at 70-80° C. under N2 for 20 min. The solution was cooled down to 0° C. and NaBH(OAc)3 (366.5 mg, 1.75 mmol) was added and the mixture was stirred at 70-80° C. under N2 for 1 h. The solution was concentrated under high vacuum and the residue was dissolved in DCM (10 mL) and the insoluble solid was filtered off. The mother liquor was dried over anhydrous Na2SO4 and concentrated to give the crude product which was purified by reverse-phase HPLC to give 1-ethyl-3-(4-(7-(4-hydroxy-cyclohexyl)-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (ye) (55.6 mg, 22%) and 1-ethyl-3-(4-(7-methyl-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (yf) (67.5 mg). 1H NMR of 41 (D6-DMSO, 400 MHz): δ 9.41 (s, 1H), 8.12 (d, J=4, 2H), 7.46 (d, J=8.8, 2H), 6.74-6.70 (m, 1H), 4.55-4.39 (m, 1H), 3.80-3.61 (m, 6H), 3.44-3.36 (m, 4H), 3.10-3.06 (m, 2H), 2.68-2.65 (m, 4H), 2.40 (s, 1H), 1.90-1.65 (m, 4H), 1.60-1.47 (m, 1H), 1.45-1.28 (m, 2H), 1.25-1.09 (m, 1H), 1.02 (t, J=7.2, 3H). LC-MS: m/z=+481 (M+H)+.

Workup

  1. temperatureThe solution was cooled down to 0° C.
  2. stirringthe mixture was stirred at 70-80° C. under N2 for 1 h
  3. concentrationThe solution was concentrated under high vacuum
  4. dissolutionthe residue was dissolved in DCM (10 mL)
  5. filtrationthe insoluble solid was filtered off
  6. dry with materialThe mother liquor was dried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customto give the crude product which
  9. customwas purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-4a7e82ba063b498fb85bd099a9ed0097
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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