HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-{5-chloro-2-[3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide

HRID 1687136
Notes
Print preview

Reaction equation

HRID 1687136 reaction equation
[NH2:1][C:2]1[CH:19]=[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:21]1[N:26]=[C:25]([NH:27][C:28]2[CH:37]=[CH:36][CH:35]=[CH:34][C:29]=2[C:30]([NH:32][CH3:33])=[O:31])[C:24]([Cl:38])=[CH:23][N:22]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>CC(O)C>[Cl:38][C:24]1[C:25]([NH:27][C:28]2[CH:37]=[CH:36][CH:35]=[CH:34][C:29]=2[C:30]([NH:32][CH3:33])=[O:31])=[N:26][C:21]([NH:1][C:2]2[CH:19]=[CH:18][C:5]3[CH2:6][CH2:7][N:8]([CH2:11][C@H:12]([OH:17])[C:13]([F:16])([F:14])[F:15])[CH2:9][CH2:10][C:4]=3[CH:3]=2)=[N:22][CH:23]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 67264395(S)-3-(7-amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,1,1-trifluoro-propan-2-ol

Product 1

HCID 668298782-{5-chloro-2-[3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide
Yield 54%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

(S)-3-(7-Amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,1,1-trifluoro-propan-2-ol (96 mg, 0.350 mmol, 1.0 eq), 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (115 mg, 0.385 mmol, 1.1 eq), and 10-camphorsulfonic acid (89 mg, 0.385 mmol, 1.1 eq) were dissolved in IPA (3 mL) and heated at 120° C. in a microwave for 40 minutes. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (20 mL) and washed with sat. NaHCO3 (20 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by amine capped silica gel chromatography using a gradient of 0-100% EtOAc/hex as the eluting solvent to obtain 2-{5-chloro-2-[3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide as a pale yellow solid (101 mg, 54%). LCMS (m/e) 535 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 11.09 (s, 1H), 8.67 (d, 1H, J=8.4 Hz), 8.11 (s, 1H), 7.51 (d, 1H, J=7.8 Hz), 7.48-7.42 (m, 1H), 7.40 (s, 1H), 7.31-7.26 (m, 1H), 7.14-7.08 (m, 1H), 7.05 (d, 1H, J=8.0 Hz), 6.91 (s, 1H), 6.21 (bs, 1H), 4.42 (bs, 1H), 4.10-4.02 (m, 1H), 3.05 (d, 3H, J=4.6 Hz), 3.00-2.80 (m, 7H), 2.78-2.64 (m, 3H).

Workup

  1. concentrationThe reaction was then concentrated under reduced pressure
  2. washwashed with sat. NaHCO3 (20 mL)
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by amine
  7. customcapped silica gel chromatography

Sources & evidence

ORD record
ord-87ece579977c46b3a55f6ad9521f96b2
Source dataset
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08148391B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes