Morpholine → HCID 90002224, compound

HRID 1771401Notes

Reaction equation

HRID 1771401 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][N:24]=[C:23]4[C:29](O)=[O:30])[N:14]=2)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1>C1COCC1>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][N:24]=[C:23]4[C:29]([N:65]3[CH2:70][CH2:69][O:68][CH2:67][CH2:66]3)=[O:30])[N:14]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8083Morpholine2×HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 90002735HCID 90002735, compound

Product 1

HCID 90002224HCID 90002224, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the carboxylic acid described above (460 mg, 80% pure, 0.90 mmol) in THF (6.0 mL) at RT was added HATU (613 mg, 1.61 mmol) and DIPEA (0.340 μL, 1.97 mmol). After 10 min the resulting mixture was treated with morpholine (0.141 mL, 1.61 mmol) and after a further 16 hr at RT additional portions of HATU (170 mg, 0.45 mmol), DIPEA (80 μL, 0.45 mmol) and morpholine (39 μL, 0.45 mmol) were added. The resulting mixture was maintained at RT for a further 24 hr and was then partitioned between saturated aq. NaHCO3 (20 mL) and EtOAc (20 mL). The organic phase was separated and was washed sequentially with 1M hydrochloric acid (20 mL), water (2×30 mL) and brine (2×30 mL) and was then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, 0-100% [10% MeOH in EtOAc] in isohexane, gradient elution) to afford the title compound, Intermediate B18, as a dark purple solid (165 mg, 82% pure, 24%); Rt 1.55 min (Method 2, acidic); m/z 482 (M+H)+ (ES+). The material was used in subsequent reactions without additional purification.

Workup

  1. additionwere added
  2. customwas then partitioned between saturated aq. NaHCO3 (20 mL) and EtOAc (20 mL)
  3. customThe organic phase was separated
  4. washwas washed sequentially with 1M hydrochloric acid (20 mL), water (2×30 mL) and brine (2×30 mL)
  5. customwas then dried
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography (SiO2, 40 g, 0-100% [10% MeOH in EtOAc] in isohexane, gradient elution)

Sources & evidence

ORD record
ord-4fceb69ce9df43e5ab4e23c5191cc6e1
Source dataset
uspto-grants-2016_02
Patent number
US09249125B2

Reaction notes

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