Triethylamine → HCID 178517912, compound

HRID 1485342Notes

Reaction equation

HRID 1485342 reaction equation
[C:1]1([N:11]2[CH2:17][CH2:16][C:15]3[C:18]([OH:22])=[N:19][CH:20]=[N:21][C:14]=3[CH2:13][CH2:12]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][N:2]=1.N1C2CCNCCC=2C(O)=NC=1.[Cl:35]C1C2C(=CC=CC=2)C(Cl)=NN=1.CCN(CC)CC>CN(C=O)C.O>[Cl:35][C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:1]([N:11]2[CH2:17][CH2:16][C:15]3[C:18]([OH:22])=[N:19][CH:20]=[N:21][C:14]=3[CH2:13][CH2:12]2)=[N:2][N:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 784901,4-DichlorophthalazineHCID 178517911HCID 178517911, compoundHCID 178517914HCID 178517914, compound

Product 1

HCID 178517912HCID 178517912, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

7-Phthalazin-1-yl-6,7,8,9-tetrahydro-5H-pyrimido-[4,5-d]azepin-4-ol. A solution of 6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ol (50 mg, 0.33 mmol), 1,4-dichlorophthalazine (55 mg, 0.28 mmol), and Et3N (0.11 mL, 0.81 mmol) in DMF (5 mL) was heated at 120° C. for 2 h. The mixture was cooled to rt, diluted with water, and extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated to give 7-(4-chloro-phthalazin-1-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ol (50 mg, 55%), of which 23 mg (0.14 mmol) was treated with ammonium formate (116 mg, 1.85 mmol) and Pd(OH)2/C (14 mg, 0.08 mmol) in MeOH/dioxane (1:1; 4 mL). After 1 h at 100° C., the mixture was cooled rt, filtered through diatomaceous earth, and concentrated to give the title compound, which was carried on to Step D as in Example 1. MS (ESI−): mass calcd. for C26H28N6, 424.24; m/z found, 423.2 [M−H]−. 1H NMR (CDCl3): 9.13 (s, 1H), 8.51 (s, 1H), 8.08-8.04 (m, 1H), 7.91-7.80 (m, 3H), 7.48-7.36 (m, 4H), 6.56 (s, 1H), 4.04-3.97 (m, 2H), 3.96-3.89 (m, 2H), 3.37-3.30 (m, 2H), 3.20-3.08 (m, 2H), 1.32 (s, 9H).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-1a92a6cc8c2642359bba1ac30505059b
Source dataset
uspto-grants-2016_08
Patent number
US09422293B2

Reaction notes

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