Morpholine → HCID 16119002, compound

HRID 1094883Notes

Reaction equation

HRID 1094883 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH:11]=O)[N:6]2[N:5]=[CH:4][N:3]=1.[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(Cl)Cl>[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH2:11][N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 57955296N-{4-[4-amino-7-formyl-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N'-[2-fluoro-5-(trifluoro-methyl)phenyl]urea

Product 1

HCID 16119002HCID 16119002, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a suspension of Intermediate AW (N-{4-[4-amino-7-formyl-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoro-methyl)phenyl]urea (50 mg, 0.1 mmol)) and morpholine (0.01 ml, 0.12 mmol) in dichloroethane (3 ml) was added sodium triacetoxyborohydride (67 mg, 0.31 mmol). The reaction was stirred under N2 at rt for 16 h. The reaction mixture was diluted with CH2Cl2 and subsequently quenched with aqueous saturated NaHCO3. The organic phase was collected, dried (Na2SO4), concentrated and purified via column chromatography (95:5 v/v CH2Cl2-MeOH) to afford 26 mg of the title compound (yield 46%). 1H-NMR (DMSO-d6) 9.32 (s, 1H), 8.96 (d, J=2 Hz, 1H), 8.64 to 8.61 (dd, J=8, 2 Hz, 1H), 7.90 (s, 1H), 7.59 to 7.34 (m, 6H), 4.29 (s, 2H), 3.86 (s, 2H), 3.55 to 3.50 (m, 4H), 3.14 (s, 3H), 2.47-2.41 (m, 4H); MS [M+H]+=573.9; LCMS RT=2.53 min.

Workup

  1. customsubsequently quenched with aqueous saturated NaHCO3
  2. customThe organic phase was collected
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. custompurified via column chromatography (95:5 v/v CH2Cl2-MeOH)

Sources & evidence

ORD record
ord-774096b2f20f4d91a76584fcf5e3e4ed
Source dataset
uspto-grants-2012_03
Patent number
US08133995B2

Reaction notes

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