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Isopropanol → N-{(1R,2R)-2-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide

HRID 1687014
Notes
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Reaction equation

HRID 1687014 reaction equation
[F:1][C:2]1([F:14])[CH2:8][CH2:7][C:6]2[CH:9]=[C:10]([NH2:13])[CH:11]=[CH:12][C:5]=2[CH2:4][CH2:3]1.Cl[C:16]1[N:21]=[C:20]([NH:22][C@@H:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@H:24]2[NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[C:19]([Cl:34])=[CH:18][N:17]=1.C(O)(C)C.Cl.O1CCOCC1>>[Cl:34][C:19]1[C:20]([NH:22][C@@H:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@H:24]2[NH:29][S:30]([CH3:33])(=[O:32])=[O:31])=[N:21][C:16]([NH:13][C:10]2[CH:11]=[CH:12][C:5]3[CH2:4][CH2:3][C:2]([F:14])([F:1])[CH2:8][CH2:7][C:6]=3[CH:9]=2)=[N:17][CH:18]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 4

HCID 3776IsopropanolHCID 204431481,4-Dioxane hydrochlorideHCID 578538657,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamineHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67264447N-{(1R,2R)-2-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide
Yield 50%

Procedure

Into a microwave vial was placed 7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamine (79 mg, 0.00040 mol) and N-[(1R,2R)-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (100 mg, 0.0003 mol) in isopropyl alcohol (4 mL, 0.05 mol) with 4N HCl-dioxane (0.04 g, 0.0003 mol). The reaction was subjected to microwaves at 120° C. for 10 min. HPLC and LCMS indicated trace starting material remaining. The reaction mixture was resubjected to microwaves for an additional 10 min. A tan solid had precipitated out of solution and was collected by filtration. The solid was redissolved in methylene chloride (5 mL) and washed with sat. sodium bicarbonate (1×5 mL) and water (2×5 mL). The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo to give N-{(1R,2R)-2-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as a brown solid (75 mg, 40%). MP: 118-128° C.; 1HNMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 7.93 (s, 1H), 7.62 (s, 1H), 7.46 (d, 1H, J=8 Hz), 7.18 (d, 1H, J=8 Hz), 7.07 (d, 1H, J=8 Hz), 6.71 (d, 1H, J=8 Hz), 3.84 (m, 1H), 2.94 (s, 3H), 2.70 (m, 4H), 1.99-2.09 (m, 6H), 1.71 (m, 2H), 1.18-1.39 (m, 5H); MS (m/e) 500 (M+1).

Workup

  1. waitThe reaction mixture was resubjected to microwaves for an additional 10 min
  2. customA tan solid had precipitated out of solution
  3. filtrationwas collected by filtration
  4. dissolutionThe solid was redissolved in methylene chloride (5 mL)
  5. washwashed with sat. sodium bicarbonate (1×5 mL) and water (2×5 mL)
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6dab4e2763f24fb2abdf79d815a9c581
Source dataset
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08148391B2

Reaction notes

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