Diisopropylethylamine → HCID 71542704, compound

HRID 931639Notes

Reaction equation

HRID 931639 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:20][CH2:19][O:18][C:17]([NH2:21])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([NH2:22])[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.[Cl:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[C:26]([F:33])[CH:25]=1.O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.C(N(C(C)C)C(C)C)C>CO.CCOC(C)=O>[NH2:21][C:17]1[O:18][CH2:19][CH2:20][C@:15]2([C:4]3[C:5](=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=3)[O:8][C:9]3[C:14]2=[CH:13][C:12]([NH:22][C:28](=[O:29])[C:27]2[CH:31]=[CH:32][C:24]([Cl:23])=[CH:25][C:26]=2[F:33])=[CH:11][CH:10]=3)[N:16]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 991524-Chloro-2-fluorobenzoic acid2×HCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate2×HCID 89473219HCID 89473219, compound

Product 1

HCID 71542704HCID 71542704, compoundYield 19.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

The (S)-3-bromo-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazine]-2′,7-diamine (0.035 g, 0.097 mmol) was dissolved in MeOH (2 mL) and 4-chloro-2-fluorobenzoic acid (0.019 g, 0.107 mmol) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride hydrate (0.031 g, 0.107 mmol) were added, followed by N-ethyl-N-isopropylpropan-2-amine (0.019 mL, 0.107 mmol). After 35 min, additional 4-chloro-2-fluorobenzoic acid (0.0095 g, 0.053 mmol) and additional 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride hydrate (0.015 g, 0.053 mmol) were added. After 2 h, the reaction was taken up in EtOAc (75 mL), and the organic layer was washed with half-saturated NaHCO3 (2×10 mL), then with saturated brine (10 mL), dried over MgSO4 and concentrated. The material was purified by preparative tlc (85% EtOAc-hexane) to afford (S)—N-(2′-amino-3-bromo-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-7-yl)-4-chloro-2-fluorobenzamide (9.7 mg, 0.019 mmol). MS (m/z) 517/519 (M+H)+. 1H NMR (400 MHz, CDCl3): 8.40 (d, 1H, J=14.7 Hz), 8.31 (d, 1H, J=2.4 Hz), 8.12 (t, 1H, J=8.5 Hz), 7.91 (d, 1H, J=2.4 Hz), 7.62 (m, 2H), 7.31 (m, 1H), 7.27 (m, 1H), 7.23 (m, 1H), 4.21 (m, 1H), 4.11 (m, 1H), 1.94 (m, 1H), 1.85 (m, 1H).

Workup

  1. waitAfter 2 h
  2. washthe organic layer was washed with half-saturated NaHCO3 (2×10 mL)
  3. dry with materialwith saturated brine (10 mL), dried over MgSO4
  4. concentrationconcentrated
  5. customThe material was purified by preparative tlc (85% EtOAc-hexane)

Sources & evidence

ORD record
ord-f901f609699a47daae2b2092e4208255
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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