Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 67264540, compound

HRID 1041626Notes

Reaction equation

HRID 1041626 reaction equation
[NH2:1][C:2]1[C:19]([O:20][CH3:21])=[CH:18][C:5]2[CH2:6][CH2:7][N:8]([CH2:11][C@H:12]([OH:17])[C:13]([F:16])([F:15])[F:14])[CH2:9][CH2:10][C:4]=2[CH:3]=1.Cl[C:23]1[N:28]=[C:27]([NH:29][C@@H:30]2[C@@H:35]3[CH2:36][C@@H:32]([CH:33]=[CH:34]3)[C@@H:31]2[C:37]([NH2:39])=[O:38])[C:26]([Cl:40])=[CH:25][N:24]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>COCCO>[Cl:40][C:26]1[C:27]([NH:29][C@@H:30]2[C@@H:35]3[CH2:36][C@@H:32]([CH:33]=[CH:34]3)[C@@H:31]2[C:37]([NH2:39])=[O:38])=[N:28][C:23]([NH:1][C:2]2[C:19]([O:20][CH3:21])=[CH:18][C:5]3[CH2:6][CH2:7][N:8]([CH2:11][C@H:12]([OH:17])[C:13]([F:14])([F:15])[F:16])[CH2:9][CH2:10][C:4]=3[CH:3]=2)=[N:24][CH:25]=1

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 57522618HCID 57522618, compoundHCID 67263894HCID 67263894, compound

Product 1

HCID 67264540HCID 67264540, compoundYield 44.4%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

(S)-3-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,1,1-trifluoro-propan-2-ol (88 mg, 0.29 mmol), (1S,2S,3R,4R)-3-(2,5-Dichloro-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (89 mg, 0.30 mmol), and 10-Camphorsulfonic acid (105 mg, 0.452 mmol) in 2-Methoxyethanol (4 mL) was heated in a microwave vial at 120° C. for 4 h. The brown solution was added dropwise to a satd. sodium bicarbonate solution (10 mL) and the vial was rinsed with 2 mL water and also added. The precipitated product was allowed to stand for 30 min, filtered and washed with water (5 mL). The crude solid was chromatographed (2×12 g silica gel, 0-80% EtOAc:Hex) to afford (1S,2S,3R,4R)-3-{5-Chloro-2-[8-methoxy-3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide as a beige solid (73 mg, 44%). LCMS: 567 (M+H); MP=120-126° C.; 1H-NMR, CDCl3: 8.24 (s, 1H), 7.92 (s, 1H), 7.43 (s, 1H), 6.66 (s, 1H), 6.61 (d, 1H, J=7.9 Hz), 6.33 (m, 2H), 5.57 (br s, 1H), 5.29 (br s, 1H), 4.46 (m, 1H), 4.07 (m, 1H), 3.89 (s, 3H), 3.10 (br s, 1H), 2.8-3.0 (m, 9H), 2.70 (m, 3H), 2.53 (d, 1H, J=8.1 Hz), 2.28 (d, 1H, J=9.4 Hz), 1.68 (d, 1H, J=8.7 Hz).

Workup

  1. additionThe brown solution was added dropwise to a satd
  2. washsodium bicarbonate solution (10 mL) and the vial was rinsed with 2 mL water
  3. additionalso added
  4. filtrationfiltered
  5. washwashed with water (5 mL)
  6. customThe crude solid was chromatographed (2×12 g silica gel, 0-80% EtOAc:Hex)

Sources & evidence

ORD record
ord-88ee56cc6fdb4952a1378c8a7270f6c3
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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